Research Models

Alzheimer's Disease

There is a large ongoing effort to characterize animal models of AD in order to better understand disease pathophysiology as well as to identify models suitable for investigating potential therapeutics. By organizing information about the characterization of selected AD models, this resource conveys what is known about each one and facilitates comparison between them.

230 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathology Behavior/Cognition Other Phenotype Availability Primary Paper Visualization
Mouse Models (211)
<p>-</p>, <p>3xTg-AD</p>, <p>The LaFerla mouse</p> B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax C7BL/6;129X1/SvJ;129S1/Sv Psen1, APP, MAPT APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V Single-cell embryos from mice with knock-in of PSEN1 with the PS1M146V mutation were injected with two human transgenes (APP with the Swedish mutation and MAPT with the P30IL mutation). Transgenes integrated at a single locus under the control of the mouse Thy1.2 promoter. Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic Alzheimer's Disease Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task. The Jackson Lab; available through the JAX MMRRC Stock# 034830; Live Oddo et al., 2003 Yes
<p>-</p>, <p>5XFAD</p>, <p>APP/PS1</p>, <p>Tg6799</p>, <p>Tg-5xFAD</p> B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax C57BL/6 x SJL APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Two transgenes: mutant human APP with the APP Swedish, Florida, and London mutations and containing the 5' untranslated region driven by the mouse Thy1 promoter; and mutant human PSEN1 including the M146L and L286V mutations driven by the mouse Thy1 promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles. Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype. The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live. Oakley et al., 2006 Yes
<p>-</p>, <p>5XFAD</p>, <p>APP/PS1</p>, <p>Tg6799</p>, <p>Tg-5xFAD</p> B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax C57BL6 APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Two transgenes: mutant human APP with the APP Swedish, Florida, and London mutations and containing the 5' untranslated region driven by the mouse Thy1 promoter; and mutant human PSEN1 including the M146L and L286V mutations driven by the mouse Thy1 promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer V. Age-dependent memory deficits, motor phenotype, and reduced anxiety. Available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Research with this model is available from Scantox Neuro. Jawhar et al., 2012, Richard et al., 2015 Yes
C57BL/6J APP APP K670_M671delinsNL (Swedish), APP T714I (Austrian) Transgene-expressing mutant APP with the Swedish mutation (K670N/M671L) and the Austrian mutation (T714I) under the control of the Thy1.2 promoter. APP: Transgenic Alzheimer's Disease Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months. Unknown. Optogenetic stimulation induced epileptic seizures. Unknown Yamada et al., 2009 Yes
<p>-</p>, <p>5xFAD-sTREM2</p> 5xFAD (C57BL6) TREM2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Adeno-associated viruses (AAV2/8) expressing EGFP- and FLAG-tagged human TREM2 (amino acids 1-171) under the control of the CAG promoter were injected bilaterally into the lateral ventricles of neonatal 5xFAD mice. TREM2: Virus; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease AAV-mediated over expression of sTREM2 decreased amyloid plaque burdens and increased numbers of plaque-associated microglia in the brains of 5xFAD mice. 5xFAD mice show impaired learning and memory in the Morris water maze, but AAV-sTREM2 5xFAD mice performed as well as non-transgenic controls. Long-term potentiation at Shaeffer collateral-CA1 synapses is impaired in 5xFAD mice. AAV-mediated over expression of sTREM2 rescued LTP in AAV-sTREM2 5xFAD mice. 5xFAD mice are available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Research with 5xFAD is available from Scantox Neuro. Zhong et al., 2019 Yes
<p>-</p>, <p>AAV-sTREM2 Tau P301S</p> Tau P301S (Line PS19) TREM2, MAPT MAPT P301S Adeno-associated viruses (AAV2/8) expressing EGFP- and FLAG-tagged human TREM2 (amino acids 1-171) under the control of the CAG promoter were injected bilaterally into the hippocampi of 3-month-old male PS19 mice. Control mice received injections of AAV expressing only EGFP. TREM2: Virus; MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice. AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze. Levels of p-tau202 and p-tau396 and activity of GSK3β were lower in AAV-sTREM2 PS19 mice compared with PS19 mice who received control vector. PS19 mice are available from The Jackson Lab: Stock# 008169; Live. Research with PS19 mice is available from Scantox Neuro. Zhang et al., 2023 Yes
B6.Cg-Apoetm1.1(APOE*4)Adiuj Abca7em#2Adiuj Trem2em1Adiuj/J C57BL/6J Abca7, APOE, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the rs3752246 SNP mutation (p.A1527G) into the Abca7 gene of double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 030283. Cryopreserved. The Jackson Laboratory Yes
B6.Cg-Apoetm1.1(APOE*4)Adiuj Abca7em#1Adiuj Trem2em1Adiuj/J C57BL/6J Abca7, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-out mutation of the Abca7 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 030320. Cryopreserved. The Jackson Laboratory Yes
<p>-</p>, <p>Dan-amyloid</p>, <p>BRI2-Danish</p>, <p>ADan precursor protein</p> Tg(Prnp-ITM2B*)6Jckr and Tg(Prnp-ITM2B*)7Jckr C57BL/6J ITM2B (BRI2) BRI2: Familial Danish Dementia (FDD) duplication Transgenic mice with human BRI2 gene containing the Familial Danish Dementia (FDD) mutation under the control of the Syrian hamster prion protein promoter. The FDD mutation is a 10-nucleotide duplication in the region of the stop codon in the BRI2 gene, resulting in a C-terminally elongated protein. ITM2B (BRI2): Transgenic Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present. Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype. Adult mice fail to gain weight with age. Alopecia. Kyphosis. Available through Mathias Jucker Coomaraswamy et al., 2010 Yes
<p>-</p>, <p>5xFAD BxD</p> (B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax x BXD[strain number] C57BL/6J X BXD[strain number] APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V “AD-BXD” refers to a panel of transgenic mouse strains, created by crossing 5XFAD mice to members of the BXD genetic reference panel. 5XFAD mice carry APP (with the Swedish, Florida, and London mutations) and PSEN1 (with M146L and L286V mutations) transgenes. The BXD genetic reference panel is a set of recombinant inbred mouse strains derived from crossing the C57BL/6J and DBA/2J inbred strains. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, although the extent of plaque deposition is strain-dependent. Transgenic AD-BXD mice exhibit cognitive deficits, assessed using contextual fear conditioning. The age of onset and severity of impairment are strain-dependent. Individual AD-BXD strains are available as F1 hybrids from The Jackson Laboratory (each strain has its own stock number). Neuner et al., 2019 Yes
<p>-</p>, <p>Amyloid β (A4) precursor-like protein 2 knock-out</p>, <p>APLP2 KO</p> B6.129S7-Aplp2tm1Dbo/J 129S7,C57BL/6J; backcrossed to C57BL/6J Aplp2 Inactivation of the mouse APLP2 gene by deleting a 1.1kb region containing the promoter and exon 1 using a targeting vector containing a PGK-neomycin expression cassette for positive selection and a MC1-TK cassette for negative selection. Aplp2: Knock-Out Alzheimer's Disease Not observed. Not observed. Homozygous animals are viable, normal in size, fertile, and do not display any gross physical or behavioral abnormalities up to 22 months of age. No impairments in axonal outgrowth of olfactory neurons following bulbectomy. The Jackson Lab: Stock# 004142; Cryopreserved von Koch et al., 1997 No
APOE2 KI C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE2 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. 2-fold higher level of steady state APOE in brain and higher APOE in serum compared with APOE3 and APOE4 KI animals. Highest levels of serum cholesterol and triglycerides after a 6hr fast. No longer available through Bruce Lamb Mann et al., 2004 No
<p>-</p>, <p>E2F</p> C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε2 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
<p>-</p>, <p>APOE2 KI</p>, <p>APOE*2 KI</p> B6.Cg-Apoeem3(APOE*)Adiuj/J C57BL/6J APOE APOE2 KI mice were generated by using CRISPR/Cas9 to introduce two point mutations (leading to arginine to cysteine substitutions at amino acids 130 and 176) in an existing humanized APOE4 knock-in allele (The Jackson Laboratory Stock# 027894). APOE: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 029017. Live. The Jackson Laboratory Yes
<p>-</p>, <p>APOE2 Humanized Knock-in</p> B6.129P2-Apoetm1(APOE*2)Mae N9 129 x C57BL/6; back-crossed to C57BL/6 APOE APOE R176C (ApoE2) Targeted gene replacement of the endogenous murine APOE gene with the human APOE2 allele. Targeting construct included exons 2-4 of APOE2. APOE: Knock-In Alzheimer's Disease, Multiple Conditions None reported. White-matter integrity, as assessed by fractional anisotropy, was reported to be higher in the hippocampus and caudate putamen of year-old female APOE2 mice, compared with APOE3 females; these genotype differences were not seen in males. Findings are mixed, with some studies reporting that APOE genotype—in some cases, interacting with sex or age—affects performance in behavioral assays. Characteristics of type III hyperlipoproteinemia. Plasma cholesterol and triglyceride levels 2-3x higher than APOE3 mice. Impaired clearance of very-low-density lipoprotein (VLDL) particles. Atherosclerotic plaques. Compared with APOE3 mice, APOE2 mice exhibited higher levels of glucose uptake in the cortex and hippocampus and up-regulation of genes involved in glucose utilization. Taconic: Stock# 1547-F and 1547-M Sullivan et al., 1998 No
<p>-</p>, <p>E3F</p> C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε3 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
<p>-</p>, <p>APOE3 KI</p>, <p>APOE*3 KI</p> B6(SJL)-ApoEem2(APOE*)Adiuj/J C57BL/6J APOE CRISPR/Cas9 used to introduce a point mutation (leading to an arginine-to-cysteine substitution at amino acid 130) into an existing humanized APOE4 knock-in allele. APOE: Knock-In Alzheimer's Disease No data. No data. The Jackson Laboratory, Stock # 029018; Live The Jackson Laboratory Yes
<p>-</p>, <p>APOE3 KI</p> C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE3 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. Intermediate brain APOE and serum cholesterol levels compared with mice with knock-in of APOE4 or APOE2. No longer available through Bruce Lamb Mann et al., 2004 Yes
<p>-</p>, <p>APOE3 Humanized Knock-in</p> B6.129P2-Apoetm2(APOE*3)Mae N8 129 x C57BL/6; back-crossed to C57BL/6 APOE Targeted replacement of the endogenous mouse APOE gene with the human APOE3 allele. Targeting vector contained exons 2-4 of human APOE3. APOE: Knock-In Alzheimer's Disease, Multiple Conditions None reported. APOE3 was considered the neutral allele against which the other human APOE genotypes were compared in most studies of neurological phenotypes in Targeted Replacement mice. Data comparing Targeted Replacement mice to wild-type mice are limited. Findings are mixed, with some studies reporting that APOE genotype—in some cases, interacting with sex or age—affects performance in behavioral assays. On a standard diet, homozygous mice have normal cholesterol and triglyceride levels, but are more susceptible than wild-type animals to diet-induced atherosclerosis. Data comparing neurological phenotypes in Targeted Replacement mice to wild-type mice are sparse, but APOE3 mice resemble wild-type mice with respect to aspects of hippocampal anatomy and physiology, including LTP and neurogenesis. Taconic: Stock# 1548-F and 1548-M Sullivan et al., 1997 No
<p>-</p>, <p>E4F</p> C57BL/6J APOE The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε4 allele) sequence, flanked by loxP sites. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Available through a material transfer agreement with the Cure Alzheimer’s Fund. Huynh et al., 2019 Yes
<p>-</p>, <p>APOE4 KI</p>, <p>APOE*4 KI</p> B6(SJL)-ApoEtm1.1(APOE*4)Adiuj/J C57BL/6J APOE Mouse ApoE exons 2, 3, and most of exon 4 replaced with human APOE sequence including exons 2, 3, 4 and a portion of the 3' UTR sequence. APOE: Knock-In Alzheimer's Disease No data. No data. The Jackson Laboratory, Stock # 027894; Live The Jackson Laboratory Yes
APOE4 KI C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE4 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. Human ApoE is detectable in serum and astrocytes. Compared to mice with knock-in of APOE2 or APOE3, APOE4 mice had the lowest serum cholesterol after a 6 hour fast. No longer available through Bruce Lamb Mann et al., 2004 No
<p>-</p>, <p>APOE4 Humanized Knock-in</p> B6.129P2-Apoetm3(APOE*4)Mae N8 129 x C57BL/6, back-crossed to C57BL/6 APOE APOE C130R (ApoE4) Targeted replacement of the endogenous murine APOE gene with the human APOE4 allele; targeting construct contained exons 2–4 of APOE4. APOE: Knock-In Alzheimer's Disease, Multiple Conditions Mice do not develop amyloid plaques or neurofibrillary tangles. Genotype-dependent differences in brain structure have been reported, but findings are mixed. While some groups have found smaller hippocampal volumes, enlarged ventricles, and compromised white matter in APOE4 mice compared with APOE3, others did not observe these differences. Findings are mixed, with some studies reporting that APOE genotype—in some cases, interacting with sex or age—affects performance in behavioral assays. Increased risk of atherosclerosis. Elevated cholesterol, APOE, and APOB-48 on a high fat diet. Transcriptomic and functional evidence for increased aerobic glycolysis and decreased mitochondrial respiration in APOE4 compared with APOE3 mice. Electrophysiological and imaging studies suggest that aged APOE4 mice exhibit neural hyperactivity compared with APOE3 mice in some brain regions. Taconic: Stock# 1549-F or 1549-M Knouff et al., 1999 No
<p>-</p>, <p>APOE KO</p>, <p>APOE -/-</p>, <p>APOE TM1</p> B6.129P2-Apoetm1Unc N11 129 x C57BL/6, back-crossed to C57BL/6 APOE Inactivation of the endogenous mouse APOE by homologous recombination and insertion of a neomycin cassette. APOE: Knock-Out Alzheimer's Disease Unknown. Unknown. Viable; healthy. Undetectable ApoE protein in plasma. Plasma cholesterol 5x higher than wild-type. Artherosclerotic lesions which progress to occlusions of coronary artery by 8 months. Taconic: Stock# APOE-M and APOE-F Piedrahita et al., 1992 No
<p>-</p>, <p>B6-Tg/Thy1APP23Sdz</p> B6.Cg-Tg(Thy1-APP)3Somm/J C57BL/6 APP APP K670_M671delinsNL (Swedish) Transgene containing human APP (isoform 751) containing the Swedish (KM670/671NL) mutation under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages. Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages. Hyperactivity observed between the ages of 6 weeks to 6 months. It is not known whether this persists or resolves in older animals. Abnormalities in open field test and impaired performance on rotorod observed from 3 months. Available through The Jackson Laboratory Stock# 030504, Live Sturchler-Pierrat et al., 1997 Yes
B6.Cg-Tg(Thy1-APP)3Somm/J; Psen1tm1.1Tcs C57BL/6J APP, PSEN1 PSEN1 R278I This is a cross between APP23 mice, which overexpress APP751 with the Swedish mutation driven by the murine Thy1 promoter, and PSEN1 knock-in mice expressing human PSEN1 with the R278I mutation under the endogenous promoter. APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques. Short-term memory deficits apparent by 3-4 months as measured by the Y maze. Reduced γ-secretase activity. Available through Takaomi Saido Saito et al., 2011 Yes
<p>-</p>, <p>APP(SL)PS1KI</p>, <p>APPxPS1-Ki</p>, <p>APPSL/PS1KI</p>, <p>APP(SL)/PS1(KI)</p>, <p>APP/PS1KI</p> The PS1KI line was established in 129SV and backcrossed &gt;7 times to C57BL/6 background. The PS1KI were bred with APPSL mice on a C57BL background (two rounds) to obtain a homozygote PS1KI and heterozygote APP. APP, PSEN1 APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P This animal is a cross between a PSEN1 knock-in line and an APP over-expressing line. The PS1 knock-in line was generated by introducing two point mutations in the wild-type mouse PSEN1, corresponding to the mutations M233T and L235P. APP751SL overexpresses human APP751 carrying the London (V717I) and Swedish (K670N/M671L) mutations under the control of the Thy1 promoter. APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons. Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates. Viable and fertile. 6 month-old animals develop decreases in body weight, and a spinal deformity (kyphosis) is common. Impaired neurogenesis. Available through Thomas Bayer or Benoit Delatour Casas et al., 2004 Yes
<p>tg13592</p> C57BL/6 x DBA/2 APP Transgene consisting of the signal plus 99-amino acid carboxyl-terminal sequence (SbC) of APP under the control of a cytomegalovirus enhancer/β-actin promoter. APP: Transgenic Alzheimer's Disease No neuropathology up to age 29 months; however, pathology reminiscent of inclusion body myopathy observed at 6-12 months: Aβ-immunoreactive deposits in skeletal muscle fibers. Muscle fibers with Aβ-immunoreactive deposits increased with age and also became vacuolated. Hypoactivity. The acquisition of place learning in the Morris water maze task was impaired. Higher cytochrome oxidase activity in thalamic nuclei. High levels of Aβ peptides in the plasma. Available through Ken-ichiro Fukuchi, University of Illinois College of Medicine at Peoria Fukuchi et al., 1996 No
<p>-</p>, <p>APP-Dutch</p>, <p>Tg-APP(Dutch)</p>, <p>APP E693Q</p>, <p>APP Dutch</p> C57BL/6J-Tg(Thy1-APPDutch)#Jckr C57BL/6J APP APP E693Q (Dutch) Transgenic mice with human APP751 bearing the E693Q mutation under the murine Thy1 promoter. APP: Transgenic Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed.  Unknown. Available through Mathias Jucker Herzig et al., 2004 Yes
<p>Osaka</p>, <p>APP(OSK)-Tg</p>, <p>APP Osaka mutation transgenic</p>, <p>APPOSK-Tg mice</p>, <p>APPOSK mice</p> B6C3F1, back-crossed to C57Bl/6 APP APP E693del (Osaka) Transgenic expression of human APP695 with the Osaka mutation driven by the mouse prion promoter. APP: Transgenic Alzheimer's Disease Age-dependent accumulation of Aβ oligomers within hippocampal and cortical neurons, but negligible deposits of extracellular amyloid. Abnormal tau phosphorylation, but no overt tangle pathology. Synaptic loss and gliosis in hippocampus and cerebral cortex. Late neuronal loss in the CA3 region of the hippocampus. Memory impairment by eight months as measured by the Morris water maze. Specifically, reduced spatial reference memory in the Morris water maze compared to mice expressing comparable levels of wild-type human APP. Available from TransGenic Inc. Tomiyama et al., 2010 Yes
<p>-</p>, <p>APP KI</p>, <p>line ADF</p> Apptm1Sud/J Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl&lt;+&gt;; C57BL/6 and maintained on a mixed background APP APP K670_M671delinsNL (Swedish), APP V717I (London), APP E693Q (Dutch) Knock-in of wild-type mouse APP exon 16 (truncated after residue KM), FLAG tag (2 repeats), a stop codon, a poly A signal region from the human growth hormone gene and an additional copy of exon 16 carrying the Swedish mutation and a modified exon 17 with the London and Dutch mutations. APP: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Lab: Stock# 008390; Cryopreserved The Jackson Laboratory No
<p>-</p>, <p>App<sup>hu/hu</sup></p> Appem1Bdes C57BL6J App CRISPR/Cas9 was used to introduce the following mutations into the endogenous App gene: G676R (G5R), F681Y (F10Y), R684H (R13H), numbered according to the 770 amino-acid isoform of human APP (position within the Aβ sequence). App: Knock-In Alzheimer's Disease Unknown. Unknown. Levels of CTFβ and Aβ are elevated in the brains of these knock-in mice, compared with wild-type animals. Available through Lutgarde Serneels and The Mary Lyon Centre at MRC Harwell, Archive# HAR:010358. Serneels et al., 2020 Yes
<p>-</p>, <p>APP null</p>, <p>APP KO</p> B6.129S7-Apptm1Dbo/J C57BL/6J APP Inactivation of the mouse APP gene by replacing a 3.8 kb sequence encoding the promoter and exon 1 with a neomycin resistance cassette. APP: Knock-Out Alzheimer's Disease Elevated reactive gliosis by 14 weeks in the hippocampus and parts of the neocortex. Impaired spatial learning as measured by the water maze at 4 and 10 months. Hypoactivity and decreased locomotor activity and forelimb grip strength. Homozygous knock-out mice weigh 15-20% less than age-matched wild-type mice. The Jackson Lab: Stock# 004133; Live Zheng et al., 1995 No
B6.Cg-Apoetm1.1(APOE*4)Adiuj Appem2Adiuj Trem2em1Adiuj/J C57BL/6J APOE, App, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce a 94-bp deletion in exon 14 (APP695 numbering) of  the App gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (The Jackson Laboratory Stock# 028709). APOE: Knock-In; App: Knock-Out; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 031722. Cryopreserved. The Jackson Laboratory Yes
<p>-</p>, <p>APP<sup>NL-F/NL-F</sup></p> Apptm2.1Tcs/Apptm2.1Tcs C57BL/6 APP APP K670_M671delinsNL (Swedish), APP I716F (Iberian) Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and the Swedish and Beyreuther/Iberian mutations. APP: Knock-In Alzheimer's Disease Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. No overexpression of APP. Generates wild-type levels of AICD. Available through Takaomi Saido Saito et al., 2014 Yes
<p>-</p>, <p>APP<sup>NL-G-F/NL-G-F</sup></p>, <p>App<sup>NL-G-F</sup></p> Apptm3.1Tcs/Apptm3.1Tcs C57BL/6 APP APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and three pathogenic mutations (Swedish, Beyreuther/Iberian, and Arctic). APP: Knock-In Alzheimer's Disease Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 6 months as measured by the Y maze. No overexpression of APP. Wild-type levels of AICD. Available through Takaomi Saido Saito et al., 2014 Yes
<p>-</p>, <p>App<sup>NL-G-F</sup>/MAPT double knock-in</p>, <p>App<sup>NL-G-F</sup>/MAPT dKI</p> C57BL/6J App, MAPT APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) AppNL-G-F mice (mouse App sequence modified to contain a humanized Aβ region and the Swedish, Iberian, and Arctic mutations linked to AD) were crossed with MAPT knock-in mice (entire genomic sequence of murine Mapt, from exon 1 to exon 14, replaced with the human MAPT gene from the ATG codon of exon 1 to the 3'-untranslated region). App: Knock-In; MAPT: Knock-In Alzheimer's Disease Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to AppNL-G-F. Deficits in the Y-maze test of working memory, similar to AppNL-G-F. Compared with AppNL-G-F mice, AppNL-G-F/MAPT double knock-in mice showed accelerated propagation of pathological tau species after AD-derived tau was injected into the mouse brain. Available through Takaomi Saido, RIKEN Center for Brain Science. Saito et al., 2019, Hashimoto et al., 2019 Yes
<p>-</p>, <p>APPPS1-21</p>, <p>APP/PS1</p> B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr C57BL/6J APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 L166P Human transgenes APP KM670/671NL and PSEN1 L166P, both under the control of the Thy1 promoter. Integration site is on lower arm of chromosome 2 between 40 and 60 cm. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.  Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months. Aβ42 concentration in CSF decreases with age, with a 50% reduction by 6 months and an 80% reduction by 18 months. Aβ40 concentration also decreases, but less robustly (45% by 18 months). CSF concentration of total tau increases, starting at 6 months, and reaches a 5-fold increase by 18 months. Available through Mathias Jucker Radde et al., 2006 Yes
<p>-</p>, <p>APPswe/PSEN1dE9/MAPT</p>, <p>APPswe/PSEN1dE9/CaMKIIa-tTa/TRE-Tg21221</p> B6.C3 x B6.129 x FVB APP, PSEN1, MAPT APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APPswe/PSEN1dE9 mice were crossed with B6.129-Tg(CK-tTa) mice where the CaMKIIa promotor drives expression of tetracycline transactivator (tTA) in forebrain neurons. Offsping were then crossed to the Tg21221 line with a responder transgene of wildtype human tau. APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic Alzheimer's Disease Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed. No data. N/A APPswe/PSEN1dE9 mice available through JAX MMRRC Stock# 034829. Jackson et al., 2016 Yes
<p>-</p>, <p>App<sup>SAA</sup></p>, <p>App<sup>SAA</sup> Knock-in</p>, <p>App<sup>SAA</sup> KI</p>, <p>APP-SAA KI</p>, <p>hAbetaSAA</p>, <p>hAbeta<sup>Swe,Arc,Aus</sup></p> B6(Cg)-Apptm1.1Dnli/J C57BL/6J App APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP T714I (Austrian) Homologous recombination was used to humanize the Aβ sequence and introduce the FAD-linked Swedish, Arctic, and Austrian mutations into the murine App gene. App: Knock-In Alzheimer's Disease Homozygotes: Amyloid plaques and plaque-associated microgliosis from 4 months of age; cerebral amyloid angiopathy and dystrophic neurites from 8 months of age. Heterozygotes: Amyloid plaques at 16 months of age. Unknown. Increased levels of CSF total tau and neurofilament light chain in AppSAA homozygous mice at 8 months of age. Significant alterations of the transcriptomes and lipidomes in microglia of AppSAA homozygotes. Available from The Jackson Laboratory Stock# 034711. Xia et al., 2021 Yes
<p>-</p>, <p>Tg2576;Pdgfrβ<sup>+/-</sup></p> APPsw mice on C57BL/6; Pdgfrβ+/- mice on 129S1/SvlmJ. APP, PDGFRB APP K670_M671delinsNL (Swedish) Progeny of APPsw transgenics (Tg2576) crossed with pericyte-deficient mice. Tg2576 express human APP with the Swedish double mutation driven by the hamster prion promoter. Pericyte-deficient mice were made by disrupting the Pdgfrβ gene using a PGKneobpA expression cassette to replace a 1.8 kb genomic segment spanning the signal peptide to the second immunoglobulin domain of PDGFRβ. APP: Transgenic; PDGFRB: Knock-Out Alzheimer's Disease Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus. Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition. Progressive loss of pericytes due to reduced Pdgfrβ signaling. Early and progressive blood brain barrier breakdown, indicated by cerebral accumulation of IgG. Reduced microvascular circulation, indicated by reduced capillary length. Available through Berislav Zlokovic Sagare et al., 2013 Yes
<p>-</p>, <p>APPSwDI/NOS2 bigenic mice</p>, <p>APPSDI/NOS2KO</p>, <p>CVN</p> B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax C57BL/6J; C57BL/6N APP, NOS2 APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) APPSwDI x NOS2 knockout animals. APPSwDI transgene expresses APP (isoform 770) with Swedish, Dutch, and Iowa mutations under the control of the mouse Thy1 promoter. NOS2 was disrupted by homologous recombination. The calmodulin binding domain of NOS2 was replaced by the neomycin resistance gene and the reading frame disrupted. APP: Transgenic; NOS2: Knock-Out Alzheimer's Disease Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone. Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks. Decreased neuropeptide Y staining throughout the hippocampus, particularly in the CA3 region and subiculum. The Jackson Lab; available through the JAX MMRRC Stock# 034849; Cryopreserved. Charles River: CVN mouse Colton et al., 2008, Wilcock et al., 2008 Yes
<p>-</p>, <p>APPSw</p>, <p>hAPPSwe (line 71)</p>, <p>hAPPSwe (line 72)</p>, <p>huAPPSw</p> B6.D2-Tg(Thy1-APPSwe)71Blt; B6.D2-Tg(Thy1-APPSwe)72Blt C57BL/6, DBA/2, crossed to C57BL/6 APP APP K670_M671delinsNL (Swedish) Transgene with human APP751 with the Swedish mutation driven by the Thy1.2 promoter. APP: Transgenic Alzheimer's Disease Amyloid plaques by 17-18 months in the neocortex and hippocampus with detection of 5-10 fold more Aβ40 than Aβ42. Plaque burden significantly lower than in the double transgenic PS2APP. Lower levels of insoluble Aβ40 and Aβ42 than the PS2APP mouse at 16-18 months. Unknown. Available through Laurence Ozmen Richards et al., 2003 No
<p>R1.40</p>, <p>APP<sup>K670/M671</sup></p>, <p>R1.40-YAC</p> B6.129-Tg(APPSw)40Btla/Mmjax (129X1/SvJ x 129S1/Sv)F1-Kitl&lt;+&gt; APP APP K670_M671delinsNL (Swedish) A 650 kb YAC transgene containing the entire human APP gene and ~250 kb of flanking sequence was mutated to include the Swedish mutation (K670N/M671L). Founder animals (line R1.40) were backcrossed to C57BL/6J. APP: Transgenic Alzheimer's Disease By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months. Unknown. Increased mortality in young homozygous animals, especially females. At 3-4 months mice maintained on the C57BL/6J background exhibit spontaneous seizure-like activity as measured by EEG and are more susceptible to kainic acid-induced seizures. The Jackson Lab; available through the JAX MMRRC Stock# 034831; Cryopreserved Lamb et al., 1997 Yes
<p>-</p>, <p>APP(695)Swe</p> C3B6-Tg(APP695)3Dbo/Mmjax C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J APP APP K670_M671delinsNL (Swedish) Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain and the Swedish mutation under the control of the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age. Congenic animals showed normal reference and working memory up to 12-14 months. The Jackson Lab; available through the JAX MMRRC Stock# 034828; Cryopreserved Borchelt et al., 1996, Savonenko et al., 2003 Yes
B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/Mmjax C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J APP APP K670_M671delinsNL (Swedish) Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain carrying the Swedish mutation under the control of the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Age-dependent increase in Aβ42, with low levels at 6-14 months and high levels at 24-26 months. No cognitive impairment in tasks of reference or working memory at 12-14 months. More than half of the female hemizygous mice do not survive past 15 months of age. The Jackson Lab; available through the JAX MMRRC Stock# 034835; Cryopreserved Savonenko et al., 2003, Borchelt et al., 1996 No
<p>-</p>, <p>APP YAC Swe/Lon (line J1.96)</p>, <p>B6-J1-96</p> B6.129S4-Tg(APPSwLon)96Btla/Mmjax 129S4/SvJae-derived J1 ES cells; backcrossed to C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717I (London) A 650 kb YAC transgene containing the entire human APP gene carrying the Swedish and London mutations with ~ 250 kb of flanking sequence; founder animals (line J1.96) have a single copy of the transgene. APP: Transgenic Alzheimer's Disease No amyloid plaques observed at 2 years. Unknown. The Jackson Lab; available through the JAX MMRRC Stock# 034837; Cryopreserved Lamb et al., 1997 No
<p>-</p>, <p>APPSwe (line C3-3)/PSEN1(A246E)(line N-5)</p>, <p>APP/PS1</p>, <p>APPswe + PS1 (A246E)</p>, <p>APP + PS1</p>, <p>AP mouse</p>, <p>C3-3/N-5</p> B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/Mmjax Origin: (C57BL/6J x C3H/HeJ)F2 APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 A246E Double transgenic mice; cross of mice expressing human PSEN1 with the A246E mutation driven by the mouse prion protein promoter with mice expressing chimeric APP (isoform 695) with the Swedish mutation driven by the mouse prion promoter. Chimeric APP was created by replacing the mouse Aβ sequence with the cognate human sequence. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus. Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task. Increased irritability. The Jackson Lab: Stock# 003378; Cryopreserved Borchelt et al., 1997, Borchelt et al., 1996 Yes
<p>-</p>, <p>APPSwe(line C3-3) X PS1dE9 (line S-9)</p>, <p>C3-3/PS1-dE9</p>, <p>C3-3 x S-9</p> B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J Line C3-3: C57BL/6J; Line S-9: hybrid strain C3H/HeJ;C57BL/6J) backcrossed to C57BL/6J APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Double transgenic mice: 1) Line C3-3: mice express a chimeric mouse/human APP gene (isoform 695) carrying the Swedish mutation and 2) Line S-9: mice express a mutant human PSEN1 gene carrying the deletion of exon 9 (dE9) driven by the mouse prion promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers. Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months. At 19 months, small but significant decrease in acetylcholinesterase activity in the hippocampus and choline acetyl transferase (ChAT) in the hippocampus and cortex. The Jackson Lab; available through the JAX MMRRC Stock# 034833; Cryopreserved Savonenko et al., 2005 Yes
<p>-</p>, <p>APP/PS1</p>, <p>C57BL/6J APPswePsen1de9</p>, <p>B6.APB<sup>Tg</sup></p> B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax C57BL/6J APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on the original hybrid C57BL/6 x C3H background were backcrossed with C57BL/6J mice. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months. Gliosis and dystrophic neurites are associated with plaques. Amyloid angiopathy has been observed in the retina. Hyperactivity is apparent by 6 months. Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age. A substantial proportion of APPswe/PSEN1dE9 mice exhibit electrographic and behavioral seizures. Available from the Jackson Laboratory, JAX MMRRC Stock# 034832 (formerly Jackson Lab Stock #005864) Minkeviciene et al., 2008, Minkeviciene et al., 2009 Yes
<p>-</p>, <p>APP/PS1</p>, <p>APPswe/PS1deltaE9</p>, <p>line 85</p>, <p>APP(swe) + PSEN1DeltaE9</p>, <p>APPdE9</p>, <p>Borchelt mice</p> B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax C57BL/6;C3H APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Co-injection of a vector for chimeric mouse/human APP carrying the Swedish mutation and a second for mutant PSEN1 (deltaE9) controlled by independent mouse prion protein promoter elements. The two transgenes co-integrated and co-segragate as a single locus. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity. Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing). Kinked tail phenotype that is believed to be due to genetic background. The Jackson Lab; available through the JAX MMRRC Stock# 034829 (formerly Jackson Lab Stock # 004462); Live Jankowsky et al., 2001, Jankowsky et al., 2004 Yes
<p>-</p>, <p>NSE-APPsw</p> Origin: C57BL/6 x DBA/2 APP APP K670_M671delinsNL (Swedish) Transgene containing human APP (isoform 695) bearing the Swedish mutation under the control of neuron specific enolase (NSE) promoter. APP: Transgenic Alzheimer's Disease Increased Aβ42 in the cortex and hippocampus of 12 month old mice, but no plaques. Increased tau phosphorylation and TUNEL-stained nuclei relative to control mice. In water maze tests, 12 month old mice had longer escape latencies than age-matched control mice. Metallothionein expression was increased in brain astrocytes and was thought to attenuate Aβ-induced neurotoxicity.  Increased Cox-2 and caspase-3 compared to age-matched control mice.   Available through Yong K Kim Hwang et al., 2004 No
Knock-in of APP(V642I) Origin:C57BL/6 x CBA; chimeric mice breed to CD-1 mice APP APP V717I (London) Targeted knock-in of the V642I mutation into exon 17 of the mouse APP gene using homologous recombination and the Cre-loxP system. APP: Transgenic Alzheimer's Disease Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy. At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels. Unknown Kawasumi et al., 2004 Yes
<p>-</p>, <p>APPlon</p>, <p>APP-london</p>, <p>APPLd</p>, <p>APP-ld</p>, <p>APP(V717I)</p>, <p>APP[V717I]</p>, <p>APP.V717I</p>, <p>APP(London) (line 2)</p>, <p>APP/LD/2</p> Tg(Thy1-APPLon)2Vln/0 Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N APP APP V717I (London) Transgene containing human APP (isoform 695) with the London mutation driven by the Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology. From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression. Increased mortality (72% by day 180). Increased incidence of seizures. Available through the KU Leuven Research and Development Office; the CRO reMYND offers research services with this line. Moechars et al., 1999 Yes
<p>-</p>, <p>APPxPS1</p>, <p>APP(V717I)x PS1(A246E)</p>, <p>APP[V717I]x PS1[A246E]</p>, <p>APP.V717I x PS1.A246E</p> Tg(Thy1-APPLon)2Vln/0; Tg(Thy1-PSEN1*A246E)2Vln/0 Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N APP, PSEN1 APP V717I (London), PSEN1 A246E The transgene overexpresses the mutant human amyloid protein precursor APP (isoform 695), which bears the London (V717I) mutation, and human presenilin-1 with the A246E mutation, both under the control of the neuron-specific murine Thy1 promoter. APP: Multi-transgene; PSEN1: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology. From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression. The CRO reMYND offers research services with this line. Dewachter et al., 2000 Yes
APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line Inbred C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic) A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus. Cryopreserved. Contact Lennart Mucke Cheng et al., 2004 Yes
arcAbeta Origin: B6D2 F1 APP APP K670_M671delinsNL (Swedish), APP E693G (Arctic) Human APP695 transgene containing the Swedish (K670N/M671L) and Arctic mutation (E693G) was generated by site-directed mutagenesis. APP: Transgenic Alzheimer's Disease At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma. Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze. Deficits in synaptic plasticity, LTP, and functional connectivity as measured by resting-state fMRI. Unknown Knobloch et al., 2007 Yes
B6;CB-Tg(Thy1-PSEN1*M146V/Thy1-APP*swe)10Arte Co-injection of transgenes into B6CBF1 oocytes, back-crossed to C57BL/6 APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 M146V Co-integration of two transgenes, mutant APP carrying the K670N/M671L mutation, and mutant PSEN1 carrying the M146V mutation, both under the control of the Thy-1 promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches. Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months. Good breeding capabilities and no premature death. Taconic: Stock #16347 Willuweit et al., 2009 Yes
<p>-</p>, <p>Atg16L<sup>ΔWD</sup></p>, <p>Atg16l1<sup>E230</sup></p>, <p>Atg16L1-WD-deficient</p>, <p>Atg16L1-WD knockout</p> Mixed 129, C57BL/6 Atg16l1 Two premature stop codons were introduced after the codon for E230, in exon 6 of the Atg16L gene. Mice express a prematurely truncated version of the autophagy protein ATG16L1, missing the WD (tryptophan-aspartate) repeat domain. Atg16l1: Knock-Out Alzheimer's Disease Intracellular and extracellular Aβ deposits, but no dense-core plaques. Microgliosis and neuron loss in 2-year-old mice. Deficits in the sucrose-preference test, spontaneous alternation in the Y-maze, and novel object recognition test. Impaired long-term potentiation at CA3-CA1 synapses. Mice are available from Ulrike Mayer or Thomas Wileman. Heckmann et al., 2020 Yes
<p>-</p>, <p>BACE1<sup>fl/fl/UbcCreER</sup> X 5xFAD</p> C57BL/6J Bace1, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 5xFAD mice were crossed with Bace1fl/fl mice (Hu et al., 2018) to generate 5xFAD mice homozygous for a floxed Bace1 gene (“Bace1fl/fl/5xFAD). Bace1fl/fl/5xFAD mice were then bred to BACE1 conditional knock-out (Hu, Yan) mice. Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter. Normal contextual and cued fear conditioning, tested at 8 to 10 months of age. Deficit in long-term potentiation at Schaffer collateral–CA1 synapses in slices from 10- to 12-month-old mice, but less severe than that seen in slices from control mice (5xFAD mice homozygous for a floxed Bace1 gene). Bace1fl/fl not yet available. UBC-Cre-ERT2 available from The Jackson Laboratory, Stock# 007001. 5xFAD available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Hu et al., 2018 Yes
<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>fl/fl</sup>;R26CreER<sup>T2</sup>-TAM</p> C57BL6 Bace1 Mice in which exon 2 of Bace 1 is flanked by LoxP sites (Ou-Yang et al., 2018) were crossed with R26CreERT2mice (Ventura et al., 2007), which carry a transgene encoding Cre recombinase fused to the estrogen receptor, inserted at the ROSA26 locus. Bace1: Conditional Knock-out Alzheimer's Disease Defects in axonal organization. Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations. BACE1fl/fl available through Robert Vassar; R26CreERT2 available through The Jackson Laboratory Stock# 008463, Live Ou-Yang et al., 2018 Yes
<p>-</p>, <p>BACE1 cKO</p>, <p>BACE1<sup>fl/fl/UbcCreER</sup></p> C57BL/6J Bace1 These mice were generated by crossing Bace1fl/fl mice (Hu et al., 2018), in which exon 2 of the mouse Bace1 gene is flanked by loxP sites, with UBC-Cre-ERT2 mice (The Jackson Laboratory, Stock# 007001), which carry a transgene encoding Cre recombinase fused to a modified human estrogen receptor, driven by the ubiquitin C promoter. Bace1: Conditional Knock-out Alzheimer's Disease No gross morphological changes observed. BACE1-deficient mice and Bace1fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age. Impaired long-term potentiation at Schaffer collateral–CA1 synapses in slices obtained from 10- to 12-month-old mice. Bace1fl/fl not yet available. UBC-Cre-ERT2 available from The Jackson Laboratory, Stock# 007001. Hu et al., 2018 Yes
<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>fl/fl</sup>;CamKIIα-iCre</p> C57BL6 Bace1 Mice in which exon 2 of Bace1 is flanked by LoxP sites (BACE1fl/fl) were crossed with mice carrying a transgene encoding Cre recombinase driven by the CamKIIα promoter (Casanova et al., 2001). Bace1: Conditional Knock-out Alzheimer's Disease Hypomyelination and defects in axon organization. Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments. Spontaneous behavioral seizures and epileptiform discharges in EEGs. BACE1fl/fl available through Robert Vassar;  CamKIIα-iCre available through the European Mouse Mutant Archive (EMMA) ID# EM: 01153, cryopreserved, sperm Ou-Yang et al., 2018 Yes
<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>flox/flox</sup>;RosaCreERT2<sup>+/WT</sup></p> C57BL/6-Bace1tm1.1mrl C57BL/6N Bace1 Mice in which exon 2 of Bace1 is flanked by LoxP sites were crossed with R26-CreERT2 mice, which carry a transgene encoding Cre recombinase fused to the estrogen receptor, inserted at the ROSA26 locus. Bace1: Conditional Knock-out Alzheimer's Disease None observed: hippocampal mossy fiber organization and sciatic-nerve myelination were normal. Performed similarly to controls in a battery of tests (Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition task). Deficit in long-term potentiation at Schaffer collateral–CA1 synapses. BACE1flox/flox available through Taconic Model# 8263, Cryopreserved. RosaCreERT2 (R26-CreERT2) available through The Jackson Laboratory Stock# 008463, Live.  Lombardo et al., 2019 Yes
<p>-</p>, <p>BACE1<sup>-/-</sup></p>, <p>BACE1 KO</p> B6.129-Bace1tm1Pcw/J C57BL/6J BACE1 Homologous recombination was used to disrupt a 2kb section of BACE1 containing exon 1 replacing it with a neomycin selection cassette and the HSV thymidine kinse gene. BACE1: Knock-Out Alzheimer's Disease Hypomyelination in the hippocampus and cerebral cortex, but normal axonal development. Increased thermal pain sensitivity as measured by a hot plate test. Decreased grip strength. Homozygous mice are viable, fertile, normal in size. No BACE1 protein is detected by Western blot. Primary cultures of cortical neurons do not secrete Aβ1-40/42, Aβ11-40/42 or β-C terminal fragments (β-CTFs). The Jackson Lab: Stock# 004714; Live Cai et al., 2001 No
<p>-</p>, <p>BACE2delta6</p>, <p>BACE2 KO</p> B6;129P2-Bace2tm1Bdes/J Strain of origin: 129P2/OlaHsd BACE2 Cre mediated recombination was used to remove exon 6 of BACE2. A targeting vector containing a loxP site and hygromycin resistance gene flanked by FRT sites was introduced into intron 5 and a second loxP site was inserted within intron 6. Heterozygous mice were crossed with mice expressing Cre under the ubiquitous phosphoglycerate kinase promoter to delete exon 6 in progeny. BACE2: Knock-Out Alzheimer's Disease Not observed. Not observed. BACE2 deficient fibroblasts produced higher levels of Aβ compared with wild-type cells. The Jackson Lab: Stock# 005618; Cryopreserved Dominguez et al., 2005 No
BRI2-Aβ40 B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J B6C3, backcrossed to C57BL/6J to generate congenic strain Construct encodes a fusion protein of the BRI protein and Aβ40 driven by the mouse prion promoter; Aβ40 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ40. Transgenic Alzheimer's Disease No overt amyloid pathology or detergent-insoluble amyloid-β. Hemizygous mice on a mixed background (C57/B6//C3H) have intact cognition as measured by fear conditioning at 12 and 14-17 months. The Jackson Lab: Stock# 007180; Cryopreserved McGowan et al., 2005 No
BRI2-Aβ42, BRI-Abeta42 B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J B6C3, backcrossed to C57BL/6J to generate congenic strain Construct encodes a fusion protein of the BRI protein and Aβ42 driven by the mouse prion promoter. Aβ42 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ42. Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss. On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid. The Jackson Lab: Stock# 007182; Cryopreserved McGowan et al., 2005 Yes
CAST.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How CAST/EiJ APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with CAST/EiJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in hippocampal area CA1. Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in males (data from females is not available, as wild-type females are unable to perform this test). Available from The Jackson Laboratory, Stock #25973. Onos et al., 2019 Yes
<p>-</p>, <p>APOE4/Trem2*R47H/Ceacam1 knock-out</p> B6.Cg-Apoetm1.1(APOE*4)Adiuj Ceacam1em#1Adiuj Trem2em1Adiuj/J C57BL/6J APOE, Ceacam1, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-out mutation of the Ceacam1 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Labortory Stock# 028709). APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 030673. Cryopreserved. The Jackson Laboratory Yes
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Clasp2em1Adiuj Trem2em1Adiuj/J C57BL/6J Clasp2, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-in L163P mutation of the Clasp2 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 031944. Cryopreserved. The Jackson Laboratory Yes
fPS1/fPS1Δ;Nestin-Cre (PS1 cKO) C57BL6/129 PSEN1 PS1 inactivation in neuronal progenitor cells (NPCs) and NPC-derived neurons and glia was achieved by crossing a floxed PS1 mouse with a Nestin-Cre transgenic mice. PSEN1: Conditional Knock-out Alzheimer's Disease Premature differentiation of neural progenitor cells results in reduced cells and neurons. 45 percent of late-born neurons fail to migrate to their appropriate positions in the superficial cortical layers. Gross behavior deficits. Mice are small. Premature death at 2-3 months of age. Available through Jie Shen Wines-Samuelson et al., 2005 No
<p>-</p>, <p>APOE2-FAD</p>, <p>APOE2 Targeted Replacement x 5xFAD</p> C57BL/6 APOE, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE2 Targeted Replacement mice were crossed with the 5xFAD line. APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice. 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE2 Targeted Replacement mice are available through Taconic, Stock# 1547-F or 1547-M. Youmans et al., 2012 Yes
<p>-</p>, <p>APOE3-FAD</p>, <p>APOE3 Targeted Replacement x 5xFAD</p> C57BL/6 APOE, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE3 Targeted Replacement mice were crossed with the 5xFAD line. APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice. 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE3 Targeted Replacement mice are available through Taconic, Stock# 1548-F or 1548-M. Youmans et al., 2012 Yes
<p>-</p>, <p>APOE4-FAD</p>, <p>APOE4 Targeted Replacement x 5xFAD</p> C57BL/6 APOE, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE4 Targeted Replacement mice were crossed with the 5xFAD line. APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.  Age-dependent learning and memory deficits in the Y maze and Morris water maze. 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE4 Targeted Replacement mice are available through Taconic, Stock# 1549-F or 1549-M. Youmans et al., 2012 Yes
<p>-</p>, <p>APOE4 (line1)/APOE KO</p>, <p>Tg(GFAP-APOE*4)1Hol</p> B6.Cg-Apoetm1Unc Cdh18Tg(GFAP-APOE_i4)1Hol/J. Formerly: B6.Cg-Tg(GFAP-APOE_i4)1Hol Apoetm1Unc/J B6/CBA; back-crossed onto C57BL6 background APOE Transgene of human APOE4 driven by the GFAP promoter; crossed to APOE knock-out mice. APOE: Transgenic; APOE: Knock-Out Alzheimer's Disease Developing and adult mice express human APOE4 in glia and neuropil. Unknown. Mice are viable, normal in size, and do not display any gross physical or behavioral abnormalities. The Jackson Lab: Stock# 004631; Cryopreserved Sun et al., 1998 No
<p>LOAD2</p> B6.Cg-Apoetm1.1(APOE*4)Adiuj Appem#1Adiuj Trem2em1Adiuj/J C57BL/6J APOE, APP, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the G601R, F606Y, and R609H (APP695 numbering) point mutations into the App gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, Jackson Lab Stock# 028709). APOE: Knock-In; APP: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 030670. Live. The Jackson Laboratory Yes
<p>-</p>, <p>hAbeta-loxP-KI on mixed B6J and B6NJ</p> B6(SJL)-Apptm1.1Aduci/J mixed B6J; B6NJ APP Three point mutations were introduced into exon 14 (exon numbering according to APP695, with 16 exons) of the mouse App gene, to produce three amino acid substitutions within the Aβ sequence (amino acids 5 (G to R), 10 (F to Y) and 13 (R to H) of Aβ). Exon 14 is also flanked by loxP sites. APP: Knock-In Alzheimer's Disease Unknown. Unknown. Available February, 2019 from The Jackson Laboratory, Stock# 030898 The Jackson Laboratory Yes
<p>-</p>, <p>hAbeta-loxP-KI</p> B6(SJL)-Apptm1.1Aduci/J mixed C57BL/6J and C57BL/6NJ App Homologous recombination was used to humanize the Aβ sequence of the endogenous App gene and to add loxP sites flanking exon 14. App: Knock-In Alzheimer's Disease No amyloid plaques observed through 22 months of age. Accelerated formation of OC-immunoreactive and Periodic Acid Schiff-positive granules. Differed from wild-type mice in the contextual fear conditioning test by 10 months of age and in the novel object recognition task by 14 months. Impaired long-term potentiation by 18 months of age. Changes in gene expression that overlap those seen in sporadic AD. Available from The Jackson Laboratory (JAX Stock No. 030898). Baglietto-Vargas et al., 2021 Yes
C57B6/C3H BACE1 Transgene of human BACE1 driven by the prion protein (PrP) promoter. BACE1: Transgenic Alzheimer's Disease No evidence of Aβ deposition in single transgenic animals. Unknown. Unknown Lee et al., 2005 No
C57BL/6 J BACE1 Wild-type human BACE driven by the murine Thy1 promoter. BACE1: Transgenic Alzheimer's Disease Not observed. Unknown. Decreased levels of full-length mature APP and increased levels of C99 and C89. Human BACE mRNA 4x higher than endogenous murine BACE. Highest expression of human BACE protein in cortex and hippocampus, lowest in cerebellum. Available through Material Transfer Management at Novartis Bodendorf et al., 2002 No
B6(SJL)-Cr2tm1(CR2,CR1)How Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J C57BL/6J Cr2, CR1, CR2, APOE, Trem2 TREM2 R47H This mutant line was generated by crossing APOE4/Trem2*R47H mice to mice in which the endogenous Cr2 gene was replaced with human CR1 and CR2 (The Jackson Laboratory Stock# 027713). Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 031668. Cryopreserved. The Jackson Laboratory Yes
<p>-</p>, <p>human tau</p> B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J The targeted allele was created in 129S4/SvJae-derived J1 embryonic stem cells that were subsequently injected into C57BL/6 blastocysts. The transgenic allele was generated in embryos derived from a cross between Swiss Webster and B6D2F1. Mice containing both alleles were back-crossed to C57BL/6 mice . MAPT Double mutant mice were generated by mating mice that express human tau (8c mice) (Duff et al., 2000), with tau knockout mice that have a targeted disruption of exon one of tau (Tucker et al., 2001), then back-crossed to obtain mice that are homozygous for disrupted murine MAPT while carrying the human tau transgene. MAPT: Knock-Out; MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately thioflavin-S positive neurofibrillary tangles. Pathology most severe in neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some neuronal loss. Normal object-recognition memory and spatial learning/memory (as assessed by the Morris Water Maze) at four months, but impaired at 12 months (Polydoro et al., 2009).  General health, weight, basic reflexes, sensory responses, locomotor function, anxiety level, and gross motor function were not different from age-matched controls (Polydoro et al., 2009). The Jackson Lab: Stock# 005491; Live. Scantox Neuro offers research services with this line. Andorfer et al., 2003 Yes
<p>-</p>, <p>CaMKII-tTA/TRE-hTau-A152T</p> C57BL/6-Tg(tetO-MAPT*A152T)L1Lms/J C59Bl/6J MAPT MAPT A152T These bigenic mice use the CaMKIIα promoter to drive expression of tetracycline transactivator (tTA) in forebrain neurons. The responder transgene is the 1N4R isoform of human tau with the A152T mutation. Expression is constitutive unless suppressed by doxycycline. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus. Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal. Increase in basal synaptic activity and epileptiform spikes. Life span normal. Available as single transgenics: The Jackson Lab Stock# 028979 (cyropreserved) and Stock# 007004 (live) Maeda et al., 2016 Yes
<p>hTau40-AT</p>, <p>Ala152T-Tau</p>, <p>A152T-Tau</p>, <p>Tau/A152T</p> C57BL/6 MAPT MAPT A152T Human full-length tau (hTau40) isoform 2N4R with the A152T mutation expressed under the Thy1.2 promotor is located in the ROSA26 locus. MAPT: Knock-In Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses. Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal. Increase in basal synaptic transmission. Available through Eva Mandelkow Decker et al., 2016, Sydow et al., 2016 Yes
<p>-</p>, <p>Tau.P301S</p>, <p>hTAU[P301S]</p>, <p>tau[P301S]</p>, <p>Tg2541</p> Thy1-hTau.P301S (CBA.C57BL/6) CBAxC57BL/6 MAPT MAPT P301S Transgenic mice overexpressing a human tau isoform that is 383 amino acids long with four microtubule-binding repeat domains and without N-terminal inserts (4R/0N). Site-directed mutagenesis was used to introduce the P301S mutation. Transgene is under the control of the neuron-specific murine Thy-1 promoter. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis. Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months. Muscle weakness, tremor. Frequent eye inflammation. Available for academic use from Michel Goedert and for commercial use from LifeArc. Also available from The Mary Lyon Centre at MRC Harwell, Archive# HAR: 011664. The CRO reMYND offers research services with this line. Allen et al., 2002 Yes
C57BL/6J-Trem2em3(TREM2)Aduci/J C57BL/6J TREM2 Mouse genomic DNA between the start codon in exon 1 and the stop codon in exon 5 of the Trem2 gene was replaced with the corresponding human genomic DNA sequence. TREM2: Knock-In Alzheimer's Disease Register interest. The Jackson Laboratory Stock No. 038103. The Jackson Laboratory Yes
C57BL/6-Trem2em2(TREM2*R47H)Aduci/J C57BL/6 TREM2 TREM2 R47H Mouse genomic DNA between the start codon in exon 1 and the stop codon in exon 5 was replaced by the corresponding human genomic DNA sequence, and the  codon at position 47 was changed from CGC (encoding arginine) to CAC (encoding histidine). TREM2: Knock-In Alzheimer's Disease Available for pre-order. The Jackson Laboratory, Stock No. 037497. The Jackson Laboratory Yes
C57BL BACE1 Transgene expressing wild-type human BACE1 driven by the mouse Thy1 promoter. BACE1: Transgenic Alzheimer's Disease Not observed. Unknown. Transgene expressed in neurons only. No change in processing of endogenous murine APP. No longer available through Michael Willem Willem et al., 2004 No
B6.Cg-Apoetm1.1(APOE*4)Adiuj Il1rapem#1Adiuj Trem2em1Adiuj/J C57BL/6J APOE, Il1rap, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-out mutation of the Il1rap gene of double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 030304. Cryopreserved. The Jackson Laboratory Yes
<p>PDGF-APPSw,Ind</p>, <p>PDGF-hAPP695,751,770V171F, KM670/671NL</p>, <p>hAPPJ20</p>, <p>hAPP</p>, <p>Mucke mice</p> B6.Cg-Zbtb20Tg(PDGFB-APPSwInd)20Lms/2Mmjax C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. APP: Transgenic Alzheimer's Disease Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity. Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated. On the C57BL/6J background hippocampal hyperexcitability was observed and cortical and hippocampal spontaneous nonconvulsive seizures. The Jackson Lab; available through the JAX MMRRC Stock# 034836-JAX; Live Mucke et al., 2000 Yes
<p>-</p>, <p>TauP301L-JNPL3</p> Tg(Prnp-MAPT*P301L)JNPL3Hlmc C57BL/6, DBA/2, SW Mixed Background MAPT MAPT P301L Transgene for human MAPT (4R0N) with the P301L mutation driven by the mouse prion promoter. MAPT: Transgenic Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord. By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization. Eye irritiation, possibily due to carrying the Pde6brd1 retinal degeneration mutation carries Pde6brd1 mutation Taconic: Stock#2508 (homozygote)#1638 (heterozygote and wild-type) has been discontinued. Lewis et al., 2000 Yes
B6(SJL)-Kif21bem1Adiuj Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J C57BL/6J Kif21b, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a knock-in T82T mutation of the Kif21b gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 031938. Cryopreserved. The Jackson Laboratory Yes
B6J.B6N-Tc(HSA17)2Mdk/J C57BL/6J MAPT, MAPT-AS1, Mapt A 190-kb region from human chromosome 17—including MAPT (H1 haplotype), MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1. MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Unknown. Unknown. Available from The Jackson Laboratory, Stock No. 035398. Benzow et al., 2024 Yes
B6J.B6N-Tc(HSA17)1Mdk/J C57BL/6J MAPT, MAPT-AS1, Mapt A 190-kb region from human chromosome 17—including MAPT (H2 haplotype), MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1. MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Unknown. Unknown. Available from The Jackson Laboratory, Stock No. 033668. Benzow et al., 2024 Yes
<p>-</p>, <p>MAPT KI</p>, <p>hTau KI</p> C57BL/6J MAPT Homologous recombination was used to replace the entire genomic sequence of murine Mapt (from exon 1 to exon 14) with the human MAPT gene from the ATG codon of exon 1 to the 3'-untranslated region (H2 haplotype; NCBI Reference Sequence: NG_007398). MAPT: Knock-In Alzheimer's Disease, Other Tauopathy No evidence of increased neuroinflammation, neuronal death, or brain atrophy in MAPT knock-in mice, compared with wild-type mice. MAPT knock-in mice perform similarly to wild-type mice in the Y-maze test of working memory. Compared with wild-type mice, MAPT knock-in mice showed accelerated propagation of pathological tau species after AD-derived tau was injected into the mouse brain. Available through Takaomi Saido, RIKEN Center for Brain Science. Saito et al., 2019, Hashimoto et al., 2019 Yes
B6(SJL)-Mthfrem1Adiuj Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J C57BL/6J Mthfr, APOE, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the A262V mutation into the Mthfr gene of APOE4/Trem2*R47H mice—double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene. Mthfr: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 030922. Cryopreserved. The Jackson Laboratory Yes
<p>line 13</p> C57BL/6 x DBA/2F1, crossed with DBA MAPT MAPT L266V, MAPT G272V Transgene expressing human 3R tau bearing the L266V and G272V mutations under the neuronal mThy-1 promoter. MAPT: Transgenic Frontotemporal Dementia, Pick's disease, Alzheimer's Disease Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology. Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test. Increased anxiety. Unknown Rockenstein et al., 2015 Yes
<p>TASD41</p>, <p>Line 41</p>, <p>hAPPSL</p>, <p>hAPP-SL</p>, <p>AβPP751</p>, <p>mThy1-hAβPP751 Swe Lon (line 41)</p>, <p>APP751SL</p>, <p>hAPPlon/swe line 41</p>, <p>APP41</p> mThy1-hAβPP751 Swe Lon C57BL/6 x DBA APP APP K670_M671delinsNL (Swedish), APP V717I (London) The transgene over-expresses the mutant human amyloid protein precursor (751 isoform), which bears both the Swedish (K670N/M671L) and the London (V717I) mutations, under the control of the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region. Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration. Available through Eliezer Masliah. The CRO PsychoGenics offers research services with this line. Rockenstein et al., 2001 Yes
Origin: C57BL/6J; backcrossed with murine APOE-null mice APOE ApoE3 minigene driven by the rat neuron-specific enolase promoter. APOE: Transgenic Alzheimer's Disease Human ApoE3 protected against the age-dependent neurodegeneration seen in APOE -/- mice. Unknown. Widespread neuronal expression of ApoE in the brain. Expression of ApoE3 protected against kainic acid-induced neuronal damage (loss of synaptophysin-positive presynaptic terminals and MAP2-positive neuronal dendrites in the neocortex and hippocampus, and a disruption of neurofilament-positive axons in the hippocampus). Available through Robert Mahley Raber et al., 1998 No
Origin: C57BL/6J; backcrossed with murine ApoE-null mice APOE The ApoE4 minigene driven by the rat neuron-specific enolase promoter. APOE: Transgenic Alzheimer's Disease Not observed. NSE-ApoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and seen primarily in females. Neuronal ApoE expression was widespread in the brain. Expression of ApoE4 did not protect against kainic acid-induced neuronal damage. Available through Robert Mahley Raber et al., 1998 No
JU.Tg(NSE-APP751)Cordell JU (Developed by Eric Bradford at University of California, Davis) APP Transgene expresses wild-type human APP751 isoform under the control of the rat neural-specific enolase (NSE) promoter. APP: Transgenic Alzheimer's Disease Age-dependent increase in Aβ deposits and tau immunoreactivity. Learning and memory deficits are age-dependent as assessed on spontaneous alternation in a Y maze and in the water-maze task. Extinct Quon et al., 1991 Yes
C57BL/6× DBA/2 PSEN2 PSEN2 N141I Transgene containing human PSEN2 carrying the N141I mutation driven by the neuron-specific enolase (NSE) promoter. PSEN2: Transgenic Alzheimer's Disease Not observed. Behavioral deficits in the water maze at 12 months in mice expressing mutatnt as well as wild-type PSEN2, including longer escape latencies than wild-type mice, but no difference in swimming speed. Expression of PSEN2 was higher in mice expressing mutant as well as wild-type PSEN2 compared to age-matched, non-transgenic mice. Alterations in levels of Aβ42, caspase-3 and Cox-2 proteins. Unknown Hwang et al., 2002 No
<p>-</p>, <p>Mouse model of pathological Rab5 activation</p> C57BL/6J RAB5A Mice carry a transgene encoding myc-tagged human Rab5a, under the control of a Thy-1 promoter. RAB5A: Transgenic Alzheimer's Disease Enlarged Rab5-positive endosomes, tau hyperphosphorylation, synapse loss in hippocampus, and loss of basal forebrain cholinergic neurons. When tested at 6 months of age, the performance of PA-Rab5 mice differed from wild-type controls in a novel object recognition test. Available through Ralph Nixon. Pensalfini et al., 2020 Yes
<p>-</p>, <p>hAPP695Indiana</p>, <p>elan mouse</p>, <p>PDAPP</p>, <p>PD-APP</p> C57B6 x DBA2 APP APP V717F (Indiana) A PDGF-driven human APP minigene with the V717F (Indiana) mutation. The construct contained APP introns 6-8 allowing alternative splicing of exons 7 and 8. APP: Transgenic Alzheimer's Disease Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus. Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months. Alterations in sleep/wake states, thermoregulation, and motor activity.   Unknown Games et al., 1995, Rockenstein et al., 1995 Yes
APP(Swedish,Indiana), line J9, hAPPJ9, hAPPlow C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. APP: Transgenic Alzheimer's Disease Amyloid plaques at 8-10 months, but not at 2-4 months when deficits in synaptic transmission are observed. Approximately 20% of mice had plaques at 5-7 months, 50% at 8-10 months, and 100% by 21-25 months. Unknown. Deficits in synaptic transmission at 2-4 months, prior to amyloid deposition. Available through Lennart Mucke Hsia et al., 1999 No
<p>line I5</p> B6.Cg-Tg(PDGFB-APP)5Lms/J (C57BL/6 x DBA/2)F2 APP APP-WT driven by the human PDGF-β promoter; an APP transgene with the Indiana mutation was converted to wild-type by PCR primer modification. APP: Transgenic Alzheimer's Disease Expression of human APP in the brain especially in the neocortex and hippocampus. No plaques up to 24 months. Unknown. The Jackson Lab: Stock# 004662; Cryopreserved Mucke et al., 2000 Yes
<p>hAPP/hTau/hPS1</p>, <p>PLB1(Triple)</p> C57BL6 APP, MAPT, PSEN1 APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W Targeted insertion of human APP and tau sequences at the HPRT site on the X chromosome, driven by mouse CaMKII-α. Human APP (isoform 770) with the Swedish and London mutations. Human tau (isoform 2N/4R, 441 amino acids) with P301L and R406W. APP/tau-expressing animals (PLB1-double) were crossed with hPS1 (A246E) transgenic mice (Borchelt et al., 1997) to generate the triple transgenic. APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene Alzheimer's Disease Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT. Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity. Litter size and overall health were normal. Mice spent more time awake at six months and had fragmented sleep. Quantitative EEG showed heightened delta power during wakefulness and REM sleep. Available through Bettina Platt Platt et al., 2011 Yes
hBACE1 C57BL/6J, for at least six generations BACE1 Targeted insertion of a single copy of human BACE1 at the HPRT locus on the X chromosome. Transgene expression driven by the mouse CaMKII-α promoter. BACE1: Transgenic Alzheimer's Disease Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology. Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety. Breeding, litter size, and overall health are normal. Reduced body weight in knock-in animals after six months of age in males and nine months in females. Available through Bettina Platt Plucińska et al., 2014 Yes
Plcg2em1Bwef C57BL/6J Plcg2 CRISPR/Cas9 was used to introduce the P522R mutation into the endogenous mouse Plcg2 gene. Knock-in mice were bred to homozygosity. Plcg2: Knock-In Alzheimer's Disease, Dementia with Lewy Bodies, Frontotemporal Dementia Hypertrophic astrocytes in the hippocampi, revealed by GFAP immunohistochemistry. Microglial activation revealed by TSPO PET imaging. Unknown. A subset of DAM genes and genes related to Plcγ2 signaling, the neuronal cytoskeleton, and myelination are differentially expressed in the brains of knock-in mice, compared with wild-type animals. Available through Christian Haass. Takalo et al., 2020 Yes
<p>-</p>, <p>Plcg2 knock-out</p> B6(SJL)-Plcg2em2Adiuj/J C57BL/6J Plcg2 CRISPR/Cas9 was used to introduce a knock-out mutation into the mouse Plcg2 gene. Plcg2: Knock-Out Alzheimer's Disease Unknown. Unknown. Available Fall, 2018 from The Jackson Laboratory, Stock# 29910 The Jackson Laboratory Yes
B6.Cg-Apoetm1.1(APOE*4)Adiuj Plcg2em2Adiuj Trem2em1Adiuj/J C57BL/6J APOE, Plcg2, Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the p.M28L mutation (methionine to leucine at position 28) into the Plcg2 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J, The Jackson Laboratory Stock# 028709). APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 030674. Cryopreserved. The Jackson Laboratory Yes
<p>-</p>, <p>5xFAD<sup>M28L</sup></p> C57BL/6J Plcg2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Plcg2*M28L/APOE4/Trem2*R47H mice (JAX 030674) were backcrossed to C57BL/6J mice to remove the APOE4 sequence and Trem2 R47H mutation. The resulting Plcg2M28L mice were then intercrossed with 5xFAD (JAX 034848) to create mice homozygous for the Plcg2 M28L mutation and hemizygous for the 5xFAD APP and PSEN1 transgenes. Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Plaque burdens in the cortex and subiculum were elevated in 5xFADM28L mice but microglia showed less interaction with plaques, compared with 5xFAD. Six-month-old 5xFADM28L and 5xFAD mice showed similar deficits in working memory, assessed in the Y-maze. Impaired synaptic function—including deficits in basal synaptic transmission and long-term potentiation—similar to 5xFAD. Differences in microglial gene expression, compared with 5xFAD. For Plcg2M28L mice, contact Andy Tsai. 5xFAD available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Tsai et al., 2023 Yes
<p>-</p>, <p>Plcg2<sup>P522R</sup></p>, <p>Plcg2<sup>R522</sup></p> B6.Cg-Plcg2em1Msasn/J C57BL/6J Plcg2 CRISPR/Cas9 gene editing was used to introduce the P522R (c.1565 C>G ) mutation into the mouse Plcg2 gene in APOE4 Knock-In mice (JAX 027894). Correctly targeted mice were then backcrossed to C57BL/6J mice (JAX 000664) to remove the human APOE4 sequence. Plcg2: Knock-In Alzheimer's Disease Unknown. Unknown. Microglia in Plcg2*P522R mice are more abundant, simpler in shape, and have lower levels of the PLCγ2 substrate, PIP2, than microglia in wild-type mice. Sight decrease in number of dendritic spines in hippocampal CA1 of Plcg2*P522R mice, compared with wild-type mice. Available from The Jackson Laboratory, Stock# 029598. Maguire et al., 2021, Bevan et al. Yes
<p>-</p>, <p>5xFAD<sup>P522R</sup></p> C57BL/6J Plcg2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V CRISPR/Cas9 gene editing was used to introduce the P522R mutation into the mouse Plcg2 gene in APOE4 Knock-In mice (JAX 027894). Correctly targeted mice were then backcrossed to C57BL/6J mice to remove the APOE4 sequence. The resulting Plcg2R522 mice (JAX 029598) were then intercrossed with 5xFAD (JAX 034848) to create mice homozygous for the Plcg2 P522R mutation and hemizygous for the 5xFAD APP and PSEN1 transgenes. Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Plaque burdens in the cortex and subiculum were lower in 5xFADP522R mice and microglia showed increased interaction with plaques, compared with 5xFAD. The PLCγ2 P522R variant protected against deficits in the Y-maze test of working memory in 5xFAD mice. The PLCγ2 P522R variant protected against synaptic deficits in 5xFAD mice. Differences in microglial gene expression, compared with 5xFAD. Plcg2R522 available from The Jackson Laboratory, JAX Stock# 029598; 5xFAD available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Tsai et al., 2023 Yes
<p>-</p>, <p>Plcg2*P522R x APP<sup>NL-G-F</sup></p>, <p>Plcg2<sup>R522</sup> x APPNL-G-F</p>, <p>App<sup>NL-G-F</sup>R522</p> B6.Cg-Plcg2em1Msasn/J x Apptm3.1Tcs/Apptm3.1Tcs C57BL/6 Plcg2, App APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) Plcg2R522 mice (JAX 029598) were intercrossed with APPNL-G-F knock-in mice to create animals homozygous for the Plcg2 P522R mutation and the App modifications (a humanized Aβ region, and the Swedish, Iberian, and Arctic mutations linked to Alzheimer’s disease). Plcg2: Knock-In; App: Knock-In Alzheimer's Disease Sex- and region-dependent increases in plaque burden, and decreases in microglia-plaque interactions, in Plcg2*P552R x APPNL-G-F mice, compared with APPNL-G-F. Unknown. The PLCγ2 P522R variant protected against synapse loss in APPNL-G-F mice. Plcg2*P522R mice are available from The Jackson Laboratory, JAX Stock# 029598; APPNL-G-F mice are available through Takaomi Saido. Bevan et al. Yes
<p>-</p>, <p>APP(Prnp)</p>, <p>line A-2</p> B6.Cg-Tg(Prnp-APP)A-2Dbo/J C57BL/6 APP Transgene expresses human APP driven by the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Unknown. Unknown. Jackson Labs: Stock# 006006; Cryopreserved The Jackson Laboratory No
<p>-</p>, <p>PS19-TREM2<sup>CV</sup></p>, <p>PS19-T2<sup>CV</sup></p> C57BL/6 MAPT, TREM2, Trem2 MAPT P301S These mice carry a human MAPT transgene with the P301S mutation linked to frontotemporal dementia and a BAC transgene encoding the common variant of human TREM2, on a mouse-Trem2-null background. MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia Brain atrophy by 9 months of age. Increased microgliosis, astrogliosis and synapse loss, compared with PS19 mice carrying TREM2 with the R47H mutation. Not known. Increased expression of pro-inflammatory cytokines and DAM (disease-associated microglia) genes, compared with PS19 mice carrying TREM2 with the R47H mutation. PS19 mice are available from The Jackson Laboratory (Stock# 008169). TREM2 mice are available through Marco Colonna. Gratuze et al., 2020 Yes
<p>-</p>, <p>PS19-T2<sup>R47H</sup></p>, <p>PS19-TREM2<sup>R47H</sup></p> C57BL/6 MAPT, TREM2, Trem2 MAPT P301S, TREM2 R47H These mice carry a human MAPT transgene with the P301S mutation linked to frontotemporal dementia and a BAC transgene encoding the R47H variant of human TREM2, on a Trem2 knockout background. MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2. Not known. Decreased expression of pro-inflammatory cytokines and DAM (disease-associated microglia) genes, compared with PS19 mice carrying the common variant of TREM2. PS19 mice are available from The Jackson Laboratory (Stock# 008169). TREM2 mice are available through Marco Colonna. Gratuze et al., 2020 Yes
Tg(Thy1-PSEN1*A246E)2Vln/0 FVB/N PSEN1 PSEN1 A246E Transgene human PSEN1 with the A246E mutation driven by the mouse Thy1 promoter. PSEN1: Transgenic Alzheimer's Disease Histologically normal up to 2 years old by hematoxylin-eosin, silver, and thioflavin-S staining. Learning and spatial memory were unaffected in the water maze test. Neither the escape latency nor escape pathway was different from PSEN1 wild-type mice at 1 and 9 months of age. Mice are more sensitive to kainic acid displaying greater KA-induced seizure activity and neuronal damage. LTP induced by a strong stimulus was not altered, but a weak stimulation at synapses between Schaeffer’s collaterals and CA1 pyramidal neurons elicited LTP only in mutant mice. No longer available through Paul van Dun Schneider et al., 2001 No
PS1cKO, PSEN1 conditional KO fPS1/fPS1;αCaMKII-Cre CaM-Cre tg mice were generated in C57BL/6J x CBA hybrid, and then back-crossed several generations to C57BL/6J. The floxed PS1 mouse was generated in C57BL/6J and 129/Sv hybrid. PSEN1 PS1 conditional KO mice with selective deletion of PSEN1 in excitatory neurons of the forebrain beginning about 1 month of age post-natally were generated by crossing a floxed PS1 mouse with a CamKII-Cre transgenic mouse. PSEN1: Conditional Knock-out Alzheimer's Disease Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments. Subtle but significant deficits in long-term spatial memory in the Morris water maze. Available through Jie Shen Yu et al., 2001 Yes
<p>-</p>, <p>PSEN1(M146L)</p>, <p>PS1 (M146L) line 5.1</p> B6/D2/Swe/SJL mixed background PSEN1 PSEN1 M146L (A>C) Transgene containing human PSEN1 with the M146L mutation driven by the rat PDGF-β promoter. PSEN1: Transgenic Alzheimer's Disease No abnormal pathology up to 2.5 years. Elevated Aβ2(43); no effect on Aβ40. Altered mitochondrial activity. Disregulation of calcium homeostasis. No difference from wild-type mice in the “Y” maze (alternation performance or activity) at 12-14 weeks. Elevated PSEN1 expression (2-3 fold). Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with wild-type mice. Larger calcium responses to depolarization. Stronger synaptic potentiation of the CA3 to CA1 projection. Available through the Technology Transfer Office, Patents & Licensing, University of South Florida. The CRO PsychoGenics offers research services with this line. Duff et al., 1996 No
PSEN1(M146V) (line 8.9) Swiss Webster x B6D2F1 PSEN1 PSEN1 M146V Transgene containing human PSEN1 with the M146V mutation driven by the rat PDGF-β promoter. PSEN1: Transgenic Alzheimer's Disease No abnormal neuropathology up to 2.5 years. Elevated Aβ42(43). Altered mitochondrial activity and disregulation of calcium homeostasis. Unknown. Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with nontransgenic or mice transgenic for wild-type PSEN1. Available through the Technology Transfer Office, Patents & Licensing, University of South Florida Duff et al., 1996 No
PS-1 P264L knock-in R1 line of the ES cells (129 mouse strain) PSEN1 PSEN1 P264L An exon replacement strategy was used to generate mouse lines carrying a targeted mutation in their endogenous presenilin-1 gene. A proline-to-leucine substitution was targeted to codon 264 in exon 8 by homologous recombination in embryonic stem (ES) cells. Cre-lox system to remove the neomycin selection cassette from the targeted gene. PSEN1: Knock-In Alzheimer's Disease Not observed. Unknown. Unknown Siman et al., 2000 No
<p>-</p>, <p>B6.PS2APP</p>, <p>TG B6.PS2APP mice (line B6.152H)</p> Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz C57BL/6 APP, PSEN2 APP K670_M671delinsNL (Swedish), PSEN2 N141I Coinjection of two transgenes into C57/Bl/6 zygotes: Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter and human APP751 with the Swedish mutation driven by the Thy1.2 promoter. APP: Transgenic; PSEN2: Transgenic Alzheimer's Disease Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months. Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months. Decreased survival of newborn neurons in the dentate gyrus at about 4 months. Reduced endoplasmic reticulum Ca2+ and calcium dysregulation. A strong increase in LTP and post-tetanic potentiation (PTP) in hippocampal slices of 10 month old animals compared to wild-type mice. Decreased perfusion in the occipital cortex at all ages tested (10-17 months). Available through Laurence Ozmen Ozmen et al., 2009 Yes
PS2(N141I) x APPswe , hPS2(N141I) x hAPPswe Tg(Thy1-APPSwe)71Jgr x Tg(Prnp-PSEN2*N141I)30Jgr C57BL/6, DLB/2, crossed to C57BL/6 APP, PSEN2 APP K670_M671delinsNL (Swedish), PSEN2 N141I Double transgenics created by crossing APPSwe mice (transgene containing the 751 isoform of human APP with the Swedish mutation driven by the Thy1.2 promoter) with PS2(N141I) mice (tansgene containing human PSEN2 with the N141I mutation driven by the mouse prion protein promoter). APP: Transgenic; PSEN2: Transgenic Alzheimer's Disease Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition. Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze. More insoluble Aβ40 and Aβ42 than age-matched APPSwe mice at 16-18 months. Loss of metabotropic glutamate receptors (mGlu2) in certain brain regions of aged mice as demonstrated by autoradiography. Available through Laurence Ozmen Richards et al., 2003 Yes
Prp-huPS2(N141I), PS2-N141I (line 30), hPS2mut Tg(Prnp-PSEN2*N141I)30Jgr Originally generated in a B6.D2 background, then crossed into C57BL/6J. PSEN2 PSEN2 N141I Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter. PSEN2: Transgenic Alzheimer's Disease Unknown. Unknown. Ubiquitous expression of mutant transgene. Brain homogenate from 2 week-old mice had PSEN levels 1.8-2.2 fold higher than wild-type mice. Disrupted Ca2+ homeostasis, similar to that of double transgenic PS2APP mice, including a reduction in endoplasmic reticulum Ca2+ content in cultured neurons and a generally decreased response to metabotropic agonists. Available through Laurence Ozmen Richards et al., 2003 No
<p>-</p>, <p>PS1 + APP</p>, <p>PSAPP</p>, <p>APP/PS1</p>, <p>APP/PS1 double transgenic</p> B6/D2/Swe/SJL mixed background APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C) These double transgenic mice were generated by crossing mice overexpressing human APP with the Swedish mutation driven by the hamster prion protein gene promoter (the Tg2576 model) with mice overexpressing human PSEN1 with the M146L mutation driven by the PDGF-β promoter (PSEN1(M146L), line 5.1). The two transgenes segregate independently. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter,  cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation. Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels. Selective increase in brain Aβ42(43) in the double transgenics (41% increase at 6 weeks) compared to Tg2576 single transgenic, which had unchanged Aβ40 and Aβ42(43) at this age. Tg2576: Taconic (Stock #001349) and Charles River; PS1(M146L): University of South Florida Technology Transfer Office. The CRO PsychoGenics offers research services with Tg2576 and the double transgenic line. Holcomb et al., 1998 Yes
PS1/PS2 cDKO, PSEN1/PSEN2 conditional double knock-out fPS1/fPS1;αCaMKII-Cre;PS2-/- C57BL6/129 hybrid PSEN1, PSEN2 To generate forebrain-specific conditional double knockout mice lacking both PS1 and PS2 (PS cDKO) mice, floxed PS1 (fPS1), αCaMKII-Cre transgenic mice and PS2-/- mice were crossed together to obtain fPS1/fPS1;αCaMKII-Cre;PS2-/- mice. PSEN1: Conditional Knock-out; PSEN2: Knock-Out Alzheimer's Disease At 2 months the number of apoptotic neurons is elevated about 8-fold. By 6 months, about 18 percent of of cortical neurons are lost. Up-regulation of inflammatory markers and progressive astrogliosis and microgliosis in the neocortex and hippocampus. Impairments in hippocampal learning and memory as indicated by Morris water maze and contextual fear conditioning evident by 2 months and worsens with age. Increased neurogenesis in the dentate gyrus. Available through Jie Shen Saura et al., 2004 Yes
<p>-</p>, <p>PS1 conditional KO</p> B6;129P-Psen1tm1Vln/J Origin: 129P2/OlaHsd; backcrossed to C57BL/6 PSEN1 A targeting vector containing a neomycin resistance gene was inserted downstream of exon 7 of PSEN1; loxP sites were inserted on both sides of exon 7 and downstream of the neomycin resistance gene. PSEN1: Knock-Out Alzheimer's Disease No morphological abnormalities. When crossed with Cre recombinase driven by Thy1, brain levels of Aβ40 and Aβ42 decrease and C-terminal fragments of APP accumulate. When crossed with Cre recombinase driven by Thy1, no cognitive deficit in an object recognition task. When crossed with Cre recombinase driven by Thy1, LTP induction is slightly altered. The Jackson Lab: Stock# 007605; Cryopreserved Dewachter et al., 2002 No
<p>-</p>, <p>PS1<sup>-/-</sup></p>, <p>PS1-</p>, <p>PSEN1 null</p>, <p>Psen1<sup>tm1Shn</sup></p>, <p>PS1 null</p> B6.129-Psen1tm1Shn/J C57BL/6 PSEN1 A targeting construct containing a neomycin cassette was used to disrupt exons 2 and 3 of the endogenous mouse PS1 gene. PSEN1: Knock-Out Alzheimer's Disease Impaired neurogenesis. Massive neuronal loss. Hemorrhages in the CNS. Unknown. Homozygous mice die shortly after birth; heterozygous mutants are viable and fertile. Gross skeletal malformations. The Jackson Lab: Stock# 003615; Cryopreserved Shen et al., 1997 No
<p>-</p>, <p>PS1M146V KI</p>, <p>PS1M146VKI</p>, <p>The Miles W. Miller Mouse</p> B6.129-Psen1tm1Mpm/J C57BL/6 PSEN1 PSEN1 M146V Point mutations were introduced into exon 5 of the endogenous mouse PSEN1 gene altering the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively. The targeting vector contained a lox-P flanked neomycin resistance cassette and herpes simplex virus thymidine kinase genes. PSEN1: Knock-In Alzheimer's Disease Hypersensitive to kainate-induced degeneration and death of CA3, CA1 and hilar neurons. Cultured hippocampal neurons have increased vulnerability to death induced by glutamate. Disrupted calcium homeostasis. Increased oxidative stress and mitochondrial dysfunction. Unknown. Mice are viable, fertile, and normal in size. No gross physical or behavioral abnormalities. The Jackson Lab: Stock# 004193; Cryopreserved Guo et al., 1999 No
line 13, PS1(P117L) Mixed C57BL/6 and DBA/2J PSEN1 PSEN1 P117L Transgene of human PSEN1 with the P117L mutation driven by the neuron specific enolase (NSE) promoter. PSEN1: Transgenic Alzheimer's Disease No plaques or diffuse amyloid deposits at 2-3 months. Elevated generation of Aβ42. Unknown. Express human PSEN1 at 2-3x the level of endogenous murine PSEN1. Impaired neurogenesis in the hippocampus. No longer available Wen et al., 2002 No
PS1(WT), PSEN1 (wild-type) Mixed C57BL/6J, DBA/2J PSEN1 Human wild-type PSEN1 driven by neuron-specific enolase (NSE). PSEN1: Transgenic Alzheimer's Disease No pathological changes have been observed in these mice. Unknown. No longer available Wen et al., 2002 No
line G9, H163R mutant PS-1 YAC, B6-G9, PS1-YAC B6.129S4-Tg(PSEN1H163R)G9Btla/J Origin: 129S4/SvJae, backcrossed to C57BL/6 PSEN1 PSEN1 H163R A 1000 kb YAC transgene (788H12) containing the entire human PSEN1 gene with the H163R mutation. Transgene also has ~550 kb of upstream and 350 kb of downstream flanking sequences. PSEN1: Transgenic Alzheimer's Disease Elevated Aβ42 in the brain and plasma. Higher levels and earlier Aβ deposition when crossed with APP YAC line R1.40. Unknown. Alternatively spliced human PSEN1 transcripts. The Jackson Lab: Stock# 006469; Cryopreserved Lamb et al., 1999 No
<p>-</p>, <p>PS2<sup>-/-</sup></p>, <p>PSEN2 null</p>, <p>PSEN KO</p>, <p>PS2 null</p> B6.129P-Psen2tm1Bdes/J 129P2/OlaHsd derived embryonic stem cells injected into C57BL/6 blastocysts; resulting chimeric mice backcrossed to C57BL/6J PSEN2 A targeting vector containing a hygromycin resistance gene driven by the phosphoglycerate kinase promoter was used to disrupt exon 5 of PSEN2 by introducing a frame shift between exons 4 and 6. PSEN2: Knock-Out Alzheimer's Disease No gross brain abnormalities or astrogliosis. Unknown. Alveolar wall thickening, pulmonary fibrosis, mild hemorrhage in the lungs. The Jackson Lab: Stock# 005617; Cryopreserved Herreman et al., 1999 No
PWK.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How PWK/PhJ APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with PWK/PhJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques and plaque-associated gliosis by 8 months. Transgenic mice are hyperactive and aggressive. Working memory and short-term memory are intact at 7 to 8 months, as assessed by tests in the Y-maze. Available from The Jackson Laboratory, Stock #25971. Onos et al., 2019 Yes
<p>-</p>, <p>APP<sub>NLI</sub></p> 129S6FVB F1 APP APP K670_M671delinsNL (Swedish), APP V717I (London) These are bigenic mice with the CAMKII-α promoter driving expression of tetracycline transactivator (tTa) in excitatory neurons in the forebrain, and a responder transgene consisting of mutant human APP (isoform 695) carrying the Swedish and London mutations. The expression of the transgene is constitutive until suppressed by doxycycline. APP: Transgenic Alzheimer's Disease Age-associated pathology in the cerebral cortex and hippocampus starting at 8 and 10½-12½ months of age, respectively. Gliosis and hyperphosphorylated tau in the vicinity of dense-core plaques. Fibrillar oligomeric species, e.g., Aβ dimers. No transgene-related deficits seen in Morris water maze (4, 12, 21, 24, months of age) or fixed consecutive-number (23 months of age) tests. Reduced body weight at 24-27 months relative to non-Tg littermates and those expressing only tTA. Available through Karen Ashe Liu et al., 2015 Yes
<p>-</p>, <p>neuropsin-tTA x FVB-Tg(tetO-tauP301L)4510</p> 4510 mice are on an FVB background. Neuropsin-tTA mice are on a C57BL/6 background. MAPT MAPT P301L Bigenic mice made by crossing an activator line, neuropsin-tTA, with a responder line, Tg(tetO-tauP301L)4510. The neuropsin promoter drives the tetracycline transactivator (tTA) transgene preferentially in a subset of entorhinal neurons. tTA drives expression of human tau (4R0N) with the P301L mutation. Transgene expression in bigenic mice is constitutive until suppressed by doxycycline. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss. Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test. No apparent change in anxiety as assessed by the open field test. Reduced Arc induction in the hippocampus after contextual fear conditioning. Subtle differences in basal synaptic transmission with enhanced axonal excitability. Unknown. de Calignon et al., 2012 Yes
<p>-</p>, <p>rTg4510</p>, <p>rTg(tetO-TauP301L)4510</p>, <p>Tau P301L</p> 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ; Fgf14Tg(tetO-MAPT*P301L)4510Kha/J. Formerly: 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ; FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ Mixed: 129S6 (activator) X FVB (responder) MAPT MAPT P301L Bi-transgenic mice are made by crossing an activator line, CaMKIIα-tTA, with a responder line, Tg(tetO-tauP301L)4510. The CaMKIIα promoter drives the tetracycline transactivator (tTA) transgene preferentially in forebrain neurons. tTA drives expression of human tau (4R0N) with the P301L mutation. Transgene expression in bi-transgenic mice is constitutive until suppressed by doxycycline. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60 percent) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (six to eight week) suppression of transgenic tau. Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved. Homozygous mice are not viable. It should be noted that disruption of an endogenous mouse gene, caused by random insertion of the MAPT transgene, significantly contributes to the neuropathological and neurodegenerative phenotypes observed in rTg4510 mice 4510 responder line: The Jackson Lab: Stock# 015815; Activator line: The Jackson Lab: Stock# 016198. Santacruz et al., 2005, Ramsden et al., 2005, Gamache et al., 2019 Yes
<p>SAMP8</p>, <p>SAMP-8</p>, <p>SAM-P/8</p>, <p>SAM-P8</p> AKR/J, suspected outbreeding to unknown line One of several related strains developed from an AKR/J inbred line with a spontaneous accelerated aging phenotype. Spontaneous Alzheimer's Disease Age-associated increase in hippocampal Aβ from 4 to 12 months, but no plaque-like structures by Congo red or thioflavine S. Spongiform degeneration: vacuoles of various size in the neuropil in the brain stem. Microglial cell proliferation. Degeneration of dopamine neurons in the substantia nigra and noradrenaline neurons in the locus coeruleus. Age-associated behavioral impairments including learning and memory difficulties, emotional disorders (reduced anxiety-like behavior and depressive behavior) and altered circadian rhythms of spontaneous motor activity and drinking behaviours. Envigo (formerly Harlan): SAMP8-TaHsd Yagi et al., 1988 No
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Snx1em1Adiuj Trem2em1Adiuj/J C57BL/6J Snx1, APOE, Trem2 TREM2 R47H CRISPR/cas9 was used to generate a D465N mutation in the Snx1 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. Snx1: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 031942. Cryopreserved. The Jackson Laboratory Yes
B6.Cg-Sorl1em1Adiuj/J C57BL/6J Sorl1 SORL1 A528T (SNP 13) CRISPR/Cas9 gene editing was used to introduce the A528T missense mutation and a silent mutation (R529R) into the mouse Sorl1 gene in APOE4/Trem2*R47H mice (JAX 028709). Correctly targeted mice were then backcrossed to C57BL/6J mice (JAX 000664) to remove the human APOE4 sequence and the Trem2 mutation. Sorl1: Knock-In Alzheimer's Disease Available from The Jackson Laboratory, JAX Stock# 032759; cryorecovery. The Jackson Laboratory Yes
B6(SJL)-Apoetm1.1(APOE*4)Adiuj Sorl1em1Adiuj Trem2em1Adiuj/J C57BL/6J Sorl1, APOE, Trem2 TREM2 R47H, SORL1 A528T (SNP 13), APOE C130R (ApoE4) CRISPR/cas9 was used to generate a knock-in A528T mutation of the Sorl1 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene. Sorl1: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Laboratory, Stock# 031940. Cryopreserved. The Jackson Laboratory Yes
<p>-</p>, <p>Rosa26<sup>TgSORL1WT</sup></p> Rosa26TgSORL1WT C57BL/6J SORL1 SORL1 cDNA downstream of the cytomegalovirus early enhancer/chicken β-actin promoter and a floxed neomycin resistance cassette with a polyA stop element (neo-R) was introduced into the murine Rosa26 locus. Cre-mediated excision of neo-R induces SORL1 overexpression. SORL1: Transgenic Alzheimer's Disease Unknown. Normal performance in the Morris Water Maze. Altered transciptome and phosphoproteome compared with wild-type mice. LTP and Morris Water Maze performance are insensitive to Aβ oligomers. Available through Thomas Willnow. Caglayan et al., 2014 Yes
<p>-</p>, <p>Sorl1 knockout</p>, <p>Sorl1<sup>-/-</sup></p>, <p>Lr11<sup>-/-</sup></p>, <p>Lr11<sup>ΔEx4</sup></p> Generated on a mixed 129SvEmcTer X C57BL/6N genetic background, subsequently backcrossed to C57BL/6J. Sorl1 The 5' region of exon 4 of the murine Sorl1 gene was replaced by a neomycin resistance cassette. The disrupted allele is expressed, and mice generate low levels of a dysfunctional SORLA protein lacking 54 amino acids within the N-terminal region of the VPS10P domain. Sorl1: Knock-Out Alzheimer's Disease Mice do not generate amyloid plaques. Disrupted nigrostriatal connectivity and thinner inner nuclear layer of the retina. Hyperactivity and reduced anxiety, compared with wild-type mice. Deficits in salt homeostasis, lowered mean arterial blood pressure, decreased fat, and increased lean body mass. Increased neuronal ERK signaling and enhanced adult neurogenesis. Available through Thomas Willnow. Andersen et al., 2005, Dodson et al., 2008 Yes
thy1-APPswe Transgene injected into C57BL/6 x C3H oocytes, some backcrossing to C57BL/6 APP APP K670_M671delinsNL (Swedish) Transgene expresses human APP (isoform 695) harboring the Swedish mutation, driven by the murine Thy-1 promoter. APP: Transgenic Alzheimer's Disease Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes. Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning. No differences in body temperature, locomotor activity, or Rotarod performance, relative to non-Tg controls. Unknown Richardson et al., 2003 Yes
<p>TAS10 x TPM</p>, <p>APPswe x PS1.M1466V</p>, <p>TAS/TPM</p> TAS10 transgene originally injected into C57BL/6 x C3H oocytes, with some backcrossing to C57BL/6. TPM generated on pure C57BL/6 background. APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 M146V This is a double transgenic model generated by crossing TAS10 mice (an APP transgenic line expressing human APP695 with the Swedish mutation) with TPM mice (a PSEN1 transgenic expressing human PSEN1 with the M146V mutation). Both transgenes are driven by the murine Thy-1 promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Aβ deposits beginning at 3 months of age, with fibrillar plaques by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid. Plaques surrounded by dystrophic neurites and reactive glia. No tangles or neuronal loss. Female mice have more rapid and severe amyloid pathology. Age-dependent impairment in object recognition memory starting around 6 months of age.  Unknown Howlett et al., 2004 Yes
Tau(WT) transgenic (line 264) B6C3F1 embryos, backcrossed to C57BL/6 MAPT This transgenic mouse expresses 3-repeat (3R) and 4-repeat (4R) isoforms of wild-type human tau. The minigene, driven by the mouse CAMKIIα promoter, includes intronic sequences flanking exon 10, allowing for physiological splicing of exon 10. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy No overt neuropathology even at the advanced age of 24 months. Comparable to non-Tg mice in Morris water maze tasks at 4 and 6 months of age. Available through Hiroshi Mori and Takami Tomiyama Umeda et al., 2013 No
C57BL/6 (75%) and 129/Ola (25%). MAPT A fragment of human tau (187-441 a.a.) expressed under control of the human tau promotor was inserted at the Hprt locus. MAPT: Transgenic Progressive Supranuclear Palsy, Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Progressive tau pathology in the hippocampus, including abnormally phosphorylated and misfolded tau, mislocalized tau, and tangle-like structures. Dystrophic neurites. Impaired spatial learning and memory in the Morris water maze. Early motor impairments, including abnormal limb clasping, Rotarod deficits and decreased grip strength. Muscle fibers in the quadriceps and latissimus muscles appeared to be degenerative/regenerative. Progressive spine curvature. Unknown. Bondulich et al., 2016 Yes
B6.Cg-Tg(Thy-MAPT*)2652Gds C57BL/6J MAPT This transgenic mouse overexpresses wild-type human tau (1N4R). The Thy1.2 promoter drives high levels of transgene expression in the CNS. MAPT: Transgenic Frontotemporal Dementia, Other Tauopathy, Alzheimer's Disease Extensive pretangle pathology throughout the brain (e.g. phospho- tau) but no mature neurofibrillary tangles and only mild oligomeric tau, restricted to the CA1 region of the hippocampus. Dystrophic neurites and axonal pathology (spheroids). No overt neuronal loss. Motor deficits develop with age, including decreased grip strength and impaired Rotarod performance. Cognitive deficits, indicative of impaired spatial learning and memory, as assessed by the Barnes maze. Homozygous mice have reduced body weight, reduced fertility, and premature death. Some homozygous mice also exhibit seizure activity. The MMRRC Stock# MMRRC:036717 Wheeler et al., 2015 Yes
Tau 10 + 16 , Tau(10+16 intron mutation)Tg, line 609 B6C3F1 embryos, backcrossed to C57BL/6 MAPT MAPT IVS10+16 C>T This model expresses a tau minigene driven by the mouse CAMKIIα promoter. The minigene encodes human tau 441, including partial intronic sequences flanking exon 10 of MAPT. The intronic mutation, IVS10 +16 C>T, was introduced by site-directed mutagenesis. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease, Other Tauopathy Aggregated tau in neurons of the entorhinal cortex, hippocampus, and cerebral cortex at advanced ages. Intraneuronal accumulation of tau oligomers in the hippocampus. Neuronal loss in the entorhinal cortex and hippocampus. Gliosis. Some hippocampal areas affected by age-related synaptic dysfunction and reduced synaptic density. Impaired spatial reference memory as measured by the Morris water maze by 6 months of age.  Human tau transcripts containing exon 10 are over-represented in the adult mouse brain, leading to elevated levels of 4R tau relative to 3R tau. Available through Hiroshi Mori and Takami Tomiyama Umeda et al., 2013 Yes
<p>-</p>, <p>Tau<sup>A152T</sup>-AAV</p> C57BL/6 MAPT MAPT A152T An adeno-associated viral (AAV1) vector encoding TauA152T under the control of the cytomegalovirus enhancer/chicken β-actin promoter was injected bilaterally into the lateral ventricles of neonatal C57BL/6 mice. MAPT: Virus Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Neuron loss and astrogliosis were observed in the cortices of 3-month-old mice. Compared with GFP-AAV controls, TauA152T-AAV mice showed deficits in contextual and cued fear conditioning, increased hyperactivity, and decreased rearing in the open-field test, and spent more time in the open arms of the elevated plus maze. TauA152T-AAV mice also exhibited motor impairment on the Rotarod. Unknown. Carlomagno et al., 2019 Yes
<p>Transgenic caspase-cleaved tau</p> BALB/C MAPT These transgenic mice express a truncated form of human tau (0N4R) that lacks the last 20 acids of the C-terminus, thus recapitulating the tau fragment produced by caspase cleavage (TauC3). Expression in the brain is driven by the promoter of the angiogenesis inhibitor 1 associated protein 4 (BAI1-AP4) gene. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia No significant cell loss or astrogliosis in the brain. Age-dependent reduction in synaptic proteins (e.g. synaptophysin, PSD95) by 1.3 to 3 months of age. Hyperphosphorylated tau oligomers and aggregates. Learning and memory deficits by 1.3 to 3 months of age, as assessed by the Y-maze and passive avoidance tests. No significant motor impairment. Normal lifespan. Unknown Kim et al., 2016 Yes
<p>-</p>, <p>mTau-E10-KO</p> Mixed background (BALB/c x C57B1/B6 x B6D2F1) MAPT Gene-targeted deletion of exon 10 in murine tau gene. MAPT: Knock-Out Alzheimer's Disease, Frontotemporal Dementia No overt neuropathology at 12 months of age. Age-dependent deterioration of sensorimotor functions, including coordination deficits on the Rotarod and a decrease in muscle strength. No deficits in learning or memory. Humanized splicing pattern of murine tau, leading to the production of 3R tau rather than 4R tau. No anxiety phenotype. Mice are no longer available, but frozen ES cells are available through Lars Nilsson or Astrid Gumucio Gumucio et al., 2013 No
<p>"Proaggregation mutant"</p>, <p>TauΔK</p>, <p>hTau40Δ280</p> Unknown. MAPT MAPT K280del These are bigenic mice in which the TET-OFF system is used to temporally control human tau expression in the brain. Tetracycline transactivator (tTA) is downstream of the CAMKII-α promoter, driving expression in excitatory neurons in the forebrain. tTA in turn stimulates expression of the responder transgene, full-length human tau (hTau40, 2N4R) carrying the FTD-associated deletion, ΔK280. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Abundant pre-tangle pathology, but only rare mature tangles, and only at advanced ages. Tau pathology included mislocalization of tau to the somatodendritic compartment, aggregation, and hyperphosphorylation. Unknown. Available through Eva Mandelkow. Eckermann et al., 2007 Yes
<p>-</p>, <p>Tau.P301L</p>, <p>hTau.P301L</p>, <p>Tau-4R-P301L</p>, <p>Tau(P301L)</p> Thy1-hTau.P301L FVB/N MAPT MAPT P301L These transgenic mice overexpress the human Tau-4R/2N isoform bearing the P301L mutation under the control of the neuron-specific murine Thy1 promoter. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF. Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months. Premature death around 8-12 months, preceded by weight loss, hyperkyphosis, reduced activity, and upper airway dysfunction. The CRO reMYND offers research services with this line.  Terwel et al., 2005 Yes
<p>-</p>, <p>Tau<sup>P301L</sup>-AAV</p> C57BL/6 MAPT MAPT P301L An adeno-associated viral (AAV1) vector encoding TauP301L under the control of the cytomegalovirus enhancer/chicken β-actin promoter was injected bilaterally into the lateral ventricles of neonatal C57BL/6 mice. MAPT: Virus Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Neurofibrillary tangles and gliosis, but no cortical neuron loss, at 6 months of age. Hyperactivity in the open field, decreased time spent in the center of open field, more time spent in the open arms of the elevated plus maze, and deficits in cued and contextual fear conditioning at 6 months of age. Unknown. Cook et al., 2015 Yes
<p>Line PS19</p>, <p>PS19Tg</p> B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J (C57BL/6 x C3H)F1 MAPT MAPT P301S Transgenic line expressing mutant human tau under the direction of the mouse prion protein (Prnp) promoter. The transgene codes for tau with four microtubule-binding domains and one N-terminal insert (4R/1N). MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis. Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months. Clasping and limb retraction when lifted by the tail at three months, followed by limb weakness and brain atrophy. Homozygous females do not mate. The Jackson Lab: Stock# 008169; Live. Research with this model is available from Scantox Neuro. Yoshiyama et al., 2007 Yes
<p>-</p>, <p>Triple transgenic</p>, <p>3Tg</p> B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L) C57BL/6, DBA/2; backcrossed to C57BL/6 APP, MAPT, PSEN2 APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I PS2APP mice (line B6.152H) x tau mice (line B6.TauP301L). PS2APP were generated by co-injecting two transgenic constructs: human PSEN2 (N141I mutation) and human APP (Swedish mutation) driven by the mouse prion promoter and the mouse Thy1 promoter respectively. The transgenic TauP301L mouse (line pR5) expresses the human tau40 isoform driven by the Thy1.2 promoter. APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic Alzheimer's Disease Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss. Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology. Cortex-specific deficiencies in oxidative phosphorylation. Loss of mitochondrial membrane potential. Reduced cortical ATP. Increased superoxide anions and ROS compared to wild-type. No differences in APP expression, APP cleavage or Aβ accumulation compared to PS2APP. Levels of ptau422 increased in an age-dependent manner, but levels of ptau231 did not. Available through Laurence Ozmen Grueninger et al., 2010 Yes
TgTauR406W, Tau R406W-CAMKII B6SJL/F1; backcrossed to C57BL/6J MAPT MAPT R406W Human 4-repeat tau cDNA with the R406W mutation containing myc and FLAG tags at N-and C-terminal ends, respectively, and driven by the CaMK-II promoter. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments. Impairments in contextual and cued fear conditioning at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits. No differences from wild-type in body weight, sensorimotor reflexes (acoustic startle response), or motor coordination (accelerating rotarod and pole tests).  Attenuation of the Schaffer collateral-evoked neural response in hippocampal slices. Decrease in prepulse inhibition. Higher mortality. Unknown Tatebayashi et al., 2002 Yes
<p>“Proaggregation mutant”</p>, <p>TauRDΔ</p>, <p>TauRD</p>, <p>TauRD/ΔK280</p>, <p>TauRDΔK</p> C57BL/6 MAPT MAPT K280del Regulatable expression of an abbreviated human tau sequence (amino acids 244-372) encompassing the four microtubule-binding repeat domains and carrying the ΔK280 mutation. Transgene is driven by the forebrain-specific CAMKIIα promoter. TET-OFF system in which the transgene is regulated by the tetracycline transactivator (tTA) and turned off by administration of doxycycline. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Tau aggregates and tangles as early as 2-3 months after gene expression. Gallyas silver-positive neurons abundant in the entorhinal cortex and amygdala, spreading to the neocortex by 15 months. “Ballooned” neurons. Astrogliosis. Synaptic structural changes and reduced synaptic number. Hippocampal neuronal loss. Reversible learning and memory deficits in the Morris water maze and passive avoidance test. No significant motor deficit, although slight reduction in Rotarod performance. Missorting of tau into the somato-dendritic compartment. Calcium dysregulation at synaptic boutons. Deficits in synaptic plasticity, including LTP and LTD. Unknown Mocanu et al., 2008 Yes
MAPT V337M, Tg214 B6SJL/F1 MAPT MAPT V337M Human 4-repeat tau driven by the PDGF-β promoter. Tagged with myc and Flag on the N- and C-terminals respectively. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure. Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze. The amount of mutant tau varied, but was generally less than one tenth of endogenous tau levels. In hippocampal slices there was attenuation of the Schaffer collateral-evoked neural response. Unknown Tanemura et al., 2002, Tanemura et al., 2001 Yes
Truncated beta-amyloid 42 C57BL6 APP Transgenic vector expresses a human N-terminally truncated Aβ sequence (3-42) fused to thyrotropin-releasing hormone. The transgene is under the control of the murine Thy1.2 regulatory sequence. The glutamate at position 3 of Aβ was mutated to glutamine to facilitate pyroglutamate formation by the enzyme glutaminyl cyclase. APP: Transgenic Alzheimer's Disease Intraneuronal accumulation of Aβ peptides in the hippocampus by 3 months and in cerebellar nuclei by 6 months. Marked gliosis in the hippocampus by 12 months. Very rare extracellular Aβ deposits. Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at 3 or 6 months. Early and persistent decrease in anxiety in the elevated plus maze. Comparable to wild-type in general motor coordination at 3 and 6 months as indicated by the balance-beam test, but impairment at 12 months. Available through Thomas Bayer Wittnam et al., 2012 Yes
<p>line 102</p> B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest doxycycline sensitivity relative to lines 107 and 885. Hyperactivity. The Jackson Lab; available through the JAX MMRRC Stock# 034845; Cryopreserved Jankowsky et al., 2005 No
<p>line 107</p> B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Intermediate expression of transgene and doxycycline sensitivity relative to lines 102 and 885. Hyperactivity. The Jackson Lab; available through the JAX MMRRC Stock# 034846; Cryopreserved Jankowsky et al., 2005 No
<p>line 885</p> B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest transgene expression and highest doxycycline requirement relative to lines 102 and 107. Hyperactivity. The Jackson Lab; available through the JAX MMRRC Stock# 034834; Cryopreserved Jankowsky et al., 2005 No
<p>-</p>, <p>Hsiao mice</p>, <p>App-Swe</p>, <p>App-sw</p>, <p>APP(sw)</p>, <p>APPSwe</p> B6;SJL-Tg(APPSWE)2576Kha B6;SJL Mixed Background APP APP K670_M671delinsNL (Swedish) The human APP gene (isoform 695) containing the double mutation K670N, M671L (Swedish mutation) under the control of the hamster prion protein. APP: Transgenic Alzheimer's Disease Numerous parenchymal Aβ plaques by 11-13 months with some vascular amyloid. Oxidative lipid damage, astrogliosis and microgliosis. No tangles or neuronal loss. Impaired spatial learning, working memory, and contextual fear conditioning reported at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months. Between 7 -12 weeks males become aggressive and begin to fight. Premature mortality: mortality of >20% anticipated, particularly in males. Taconic: Stock #1349. Charles RiverPsychoGenics, and Scantox Neuro offer research services with this line. Hsiao et al., 1996 Yes
<p>APPSwe-Tau</p>, <p>APPSwe(2576)/TauJNPL3</p>, <p>TAPP</p> Tg(APPSWE)2576Kha; Tg(Prnp-MAPT*P301L)JNPL3Hlmc C57BL/6, DBA/2, SJL, SW Mixed Background APP, MAPT APP K670_M671delinsNL (Swedish), MAPT P301L Generated by crossing Tg2576 mice, which have the transgene for human APP (isoform 695) carrying the Swedish mutation with mice expressing human MAPT (4 repeat) with the P301L mutation. APP; MAPT: Transgenic Alzheimer's Disease Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis. Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming. Progressive hindlimb weakness. Hunched posture. Eye irritations. Some mice have the Pde6brd1 retinal degeneration mutation which can cause light sensitivity and/or blindness and may affect behavioral testing. Taconic: Stock# 2469 Lewis et al., 2001 Yes
<p>-</p>, <p>Tg-Aβ(4-42)</p> C57BL6 APP Transgenic encodes N-truncated human Aβ (Aβ4-42) fused to the murine thyrotropin releasing hormone signal peptide under the control of the Thy1 promoter. APP: Transgenic Alzheimer's Disease Aβ4-42 is dectable starting at two months, predominantly in the CA1 region of the hippocampus, but also in the occipital cortex, piriform cortex, striatum, and superior colliculus. Age- and dose-dependent hippocampal neuronal loss is seen in the CA1 region as well as microgliosis and astrogliosis. Age-dependent spatial learning deficit as demonstrated in the Morris water maze, specifically, the absence of a preference for the target quadrant starting at eight months in homozygous mice and at 12 months in hemizygous mice. Impaired contextual fear conditioning. Intact vision and motor abilities. Available through Thomas Bayer. Bouter et al., 2013 Yes
B6CBA-Tg(Thy1.2-hAPParc) C57BL/6-CBA APP APP E693G (Arctic) Transgenic mice with human APP (isoform 695) bearing the Arctic APP mutation (E693G). APP: Transgenic Alzheimer's Disease Mild amyloid pathology with a relatively late onset, starting with intracellular Aβ, then diffuse extracellular Aβ deposits in the subiculum, expanding to interconnected brain regions such as retrosplenial granular cortex, thalamus, and mammillary bodies. Pathology more severe in females. Spatial learning and memory deficit in the Barnes maze test in heterozygous females mice at 15 months. Available through Annica Rönnbäck Rönnbäck et al., 2011 No
<p>-</p>, <p>Tg-Swe</p> C57BL/6J APP APP K670_M671delinsNL (Swedish) Transgene with human APP (isoform 695) bearing the Swedish mutation under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease Extracellular amyloid deposition begins at ~12 months. Intraneuronal Aβ aggregates at ~6 months. Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1.0% (at 12 months) and 2.8% (at 18 months). Unknown. Available through Lars Nilsson Philipson et al., 2009, Lord et al., 2006 Yes
R1 line of ES cells APP APP K670_M671delinsNL (Swedish) Modification of mouse APP sequence to introduce the Swedish mutation and "humanize" the murine Aβ sequence by altering three amino acids. APP: Knock-In Alzheimer's Disease Accumulation of human Aβ. Unknown. Unknown Reaume et al., 1996 No
<p>-</p>, <p>tg ArcSwe</p>, <p>APP-ArcSwe</p> C57BL/6J APP APP K670_M671delinsNL (Swedish), APP E693G (Arctic) Transgene with human APP (isoform 695) containing both the Arctic (E693G) and Swedish (KM670/671NL) mutations under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus. Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months. Tg-ArcSwe have reduced body weight compared with nontransgenic littermates. Available through Stina Syvänen or Lars Nilsson. Lord et al., 2006 Yes
<p>-</p>, <p>APP(swe/ind) CRND8</p> Hybrid C3H/He-C57BL/6 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Transgene contains human APP695 with the Swedish mutation (KM670/671/NL) and Indiana mutation (V717F) under the control of the hamster prion (PrP) gene promoter. The expression cassette includes about 90 nucleotides of the APP 5'-untranslated region adjacent to the start codon and 269 nucleotides of the 3′-untranslated region. APP: Transgenic Alzheimer's Disease Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months . Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests. Cholinergic dysfunction: decrease in the number of cholinergic neurons in the nucleus basalis magnocellularis by 7 months as measured by ChAT immunoreactivity. Enhanced auditory startle response and modest reduction in prepulse inhibition. Available through the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto Chishti et al., 2001 Yes
C57BL/6N APP APP K670_M671delinsNL (Swedish), APP S679C These transgenic mice express human APP (isoform 751) containing the Swedish (KM670/671NL) mutation and a serine-to-cysteine substitution at amino acid 679 (amino acid 8 within the Aβ sequence), under the control of the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, MCI due to AD Intracellular Aβ immunoreactivity in the hippocampus and cortex, beginning by 12 months. No amyloid plaques, hyperphosphorylated tau, microgliosis, astrogliosis, or neuron loss through 24 months. Learning deficits, as well as indicators of increased anxiety and depression, by 7 months. More rapid decay of hippocampal long-term potentiation, compared with wild-type mice. Age-dependent cholinergic loss in hippocampus; lower rates of serotonin turnover in hippocampus, ventral striatum, and amygdala. Available through Carsten Korth. Müller-Schiffmann et al., 2016 Yes
BRI2(Tg-FDD) Hybrid C3HeB/FeJ embryo; crossed to C57BL/6J ITM2B (BRI2) BRI2: Familial Danish Dementia (FDD) duplication The transgene, driven by the mouse prion promoter (Prnp), consists of the 795 form of human BRI(2) with a 10-nucleotide duplication-insertion (TTTAATTTGT). ITM2B (BRI2): Transgenic Familial Danish Dementia, Cerebral Amyloid Angiopathy, Alzheimer's Disease Widespread cerebral amyloid angiopathy (CAA) starting around 7 months. Deposition of the Danish amyloid subunit (ADan) in brain parenchyma and vessels, along with amyloid-associated gliosis and inflammation, intracellular and extracellular deposition of oligomeric ADan, and tau-positive deposits in neuropil, but no neurofibrillary tangles. Age-dependent abnormal grooming behavior. Around one year mice develop an arched back and walk with a wide-based gait and short steps. Feet clasping upon suspension of the mice by their tails. Available through Ruben Vidal Vidal et al., 2009 No
mAPP/DN-RAGE, APP/DN-RAGE C57BL/6 APP, RAGE (AGER) APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Mice expressing a form of transgenic RAGE comprising a truncated form of the receptor with intact extracellular and membrane-spanning portions, but a deleted cytosolic tail driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661--now extinct). APP: Transgenic; RAGE (AGER): Transgenic Alzheimer's Disease Diminished neuropathology compared with mice expressing mutant APP alone at both 3–4 and 14–18 months of age. Preservation of spatial learning and memory compared with Tg-mAPP/RAGE animals. No abnormalities with respect to reproductive fitness, development, basic neurological functioning, or longevity. Available through Shirley ShiDu Yan Arancio et al., 2004 No
APP/RAGE C57BL/6 APP, RAGE (AGER) APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Mice expressing human wild-type RAGE driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661-now extinct) APP: Transgenic; RAGE (AGER): Transgenic Alzheimer's Disease Increased activation of microglia and astrocytes compared to mice expressing mutant APP alone. Abnormalities in spatial learning and memory at 3-4 months of age, whereas deficits occur later in mice expressing mutant APP alone and are less severe. Available through Shirley ShiDu Yan Arancio et al., 2004 No
<p>APP-Swedish,Dutch,Iowa</p>, <p>APPSwDI</p> C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax C57BL/6 APP APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) Transgenic mice with 2.1 kb of the human APP gene (isoform 770) with the Swedish (K670N/M671L), Dutch (E693Q) and Iowa (D694N) mutations under the control of the mouse Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months. Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination. The Jackson Lab; available through the JAX MMRRC Stock# 034843; Live Davis et al., 2004 Yes
<p>-</p>, <p>Tau22</p> C57BL6/CBA; backcrossed to C57BL6 MAPT MAPT G272V, MAPT P301S Transgene containing the cDNA of the 412 amino acid isoform of human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2 promotor. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis. Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity. Fertile with normal frequency and size of litters. Stably transmits the transgene to offspring. Deficits in hippocampal synaptic transmission. Available through Luc Buée Schindowski et al., 2006 Yes
<p>Thy-1 mutated human tau</p>, <p>TAU 441</p>, <p>hTAU441</p>, <p>TAU441 V337M R406W</p> C57Bl/6xDBA MAPT MAPT V337M, MAPT R406W Transgene consists of human MAPT Tau441 (2N/4R) with mutations V337M and R406W under control of the Thy1 promoter. MAPT: Transgenic Alzheimer's Disease Increased total tau, and phosphorylated tau (Thr181, Ser199, Thr231) in amygdala and hippocampus starting at 3 months. Spatial memory deficits starting at 5 months (Morris water maze). Olfactory deficits at 5 months (Buried food test). No motor deficits (rota rod, beam walk) or depressive behavior (forced swim test). Olfactory deficits. The CRO Scantox Neuro offers research services with this line. Flunkert et al., 2013 Yes
Thy-1 PS1.M146V Transgene injected into fertilized oocytes from pure C57BL/6 mice. PSEN1 PSEN1 M146V Transgene encoding human PSEN1 carrying the M146V mutation. Transgene is driven by the murine Thy-1 promoter. PSEN1: Transgenic Alzheimer's Disease No plaques. Unknown. Unknown Howlett et al., 2004 No
<p>-</p>, <p>BAC-TREM2</p> FVB/NJ TREM2 The BAC (RP11-237K15) transgene contains the TREM2 coding region and surrounding genomic regions (>50 kb on each side) with conserved gene regulatory elements. Key coding exons were deleted from other TREM-like genes contained in the BAC, to prevent their expression. Transgenic mice were generated and maintained on the FVB/NJ background. TREM2: Transgenic Alzheimer's Disease No obvious neuropathology is observed at 4, 7 and 11 months of age. Normal contextual fear conditioning at 10 months of age. Normal LTP at 10 months of age. Available through X. William Yang. Lee et al., 2018 Yes
<p>-</p>, <p>BAC-TREM2 X&nbsp;5xFAD</p> TREM2-BAC: FVB/NJ; 5xFAD: C57BL/6 X SJL TREM2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V TREM2-BAC mice were crossed with 5xFAD mice. TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques with plaque-associated microgliosis. Reduced plaque burden, altered microglial and plaque morphology, and less severe plaque-associated neuritic dystrophy, compared with 5xFAD. 5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired. TREM2-BAC: Available through X. William Yang. 5xFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live Lee et al., 2018 Yes
B6(C3)-Trem2tm1c(EUCOMM)Wtsi/AdiujJ B6(C3) Trem2 Targeted insertion of LoxP sites flanking exons 2 and 3 of the mouse Trem2 gene. Trem2: Knock-In Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease No data. No data. The Jackson Lab: Stock# 029853; Live The Jackson Laboratory No
C57Bl/6J Trem2 TREM2 H157Y CRISPR/Cas9 gene editing was used to introduce the H157Y mutation into the mouse Trem2 gene. Trem2: Knock-In Alzheimer's Disease Microglial density and morphology did not differ between carriers of the H157Y variant and wild-type mice. Trem2-H157Y knock-in did not differ from wild-type mice at 6 months of age in tests of anxiety, associative memory, and spatial working memory. Enhanced hippocampal synaptic plasticity was observed in mice homozygous for the H157Y variant, compared with wild-type mice. Available through Na Zhao (zhao.na@mayo.edu). Qiao et al., 2023 Yes
C57Bl/6J Trem2, APP, PSEN1 TREM2 H157Y, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V CRISPR/Cas9 gene editing was used to introduce the H157Y mutation into the mouse Trem2 gene. The resulting Trem2-H157Y knock-in mice were then intercrossed with 5xFAD mice. Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Age-dependent effects on amyloid-β pathology and gliosis. At 4 months, plaque burdens, microgliosis, and astrogliosis were similar among genotypes. By 8.5 months, amyloid burdens, microgliosis, and astrogliosis were reduced in homozygous carriers of the H157Y variant, compared with 5xFAD mice homozygous for wild-type Trem2. Unknown. Increased TREM2 shedding, decreased TREM2 signaling, and accelerated Aβ42 clearance from the interstitial fluid in 5xFAD homozygous for Trem2 H157Y, compared with 5xFAD homozygous for wild-type Trem2. Downregulation of disease-associated microglia (DAM) genes, microglial immune-related genes, genes encoding inflammatory cytokines, and genes expressed by astrocytes in H157Y homozygotes. Trem2-H157Y knock-in mice are available through Na Zhao (zhao.na@mayo.edu). 5xFAD mice are available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Qiao et al., 2023 Yes
<p>-</p>, <p>CV<sup>+</sup>mTrem2<sup>−/−</sup></p>, <p>CV-KO</p>, <p>TREM2<sup>CV</sup></p> C57BL/6 ×CBA, backcrossed for at least four generations to C57BL/6. TREM2, Trem2 BAC transgenic mice carrying human TREM2 (common variant), TREML1, and TREML2 were backcrossed to Trem2 knockout mice to yield mice that express the common variant of human TREM2 in the absence of mouse Trem2. TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease Unknown. Unknown. TREM2 mice are available through Marco Colonna. Song et al., 2018 Yes
<p>-</p>, <p>CV<sup>+</sup>mTrem2<sup>−/−</sup>5XFAD</p> C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 Trem2, TREM2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V BAC transgenic mice carrying human TREM2 (common variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the common variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5xFAD mice. Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques surrounded by activated microglia. No data. Neurodegeneration-associated microglial activation markers elevated, compared with 5XFAD lacking TREM2. TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Song et al., 2018 Yes
<p>-</p>, <p>R47H<sup>+</sup>mTrem2<sup>−/−</sup></p>, <p>R47H-KO</p>, <p>TREM2<sup>R47H</sup></p> C57BL/6 × CBA, backcrossed for at least four generations to C57BL/6. TREM2, Trem2 TREM2 R47H BAC transgenic mice carrying human TREM2 (R47H variant), TREML1, and TREML2 were backcrossed to Trem2 knockout mice to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2. TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease Unknown. Unknown. TREM2 mice are available through Marco Colonna. Song et al., 2018 Yes
<p>-</p>, <p>R47H<sup>+</sup>mTrem2<sup>−/−</sup>5XFAD</p> C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 Trem2, TREM2, APP, PSEN1 TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V BAC-transgenic mice carrying the human TREM2 (R47H variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5XFAD mice. Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant. No data. TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Song et al., 2018 Yes
<p>-</p>, <p>Trem2-IPD</p> B6-Trem2em2Npa C57BL/6J Trem2 CRISPR/Cas9 gene editing was used to disrupt the ADAM10/17 recognition site on TREM2, changing histidine-157 to isoleucine (I), serine-158 to proline (P), and threonine-159 to aspartate (D). Trem2: Knock-In Alzheimer's Disease At 3 months of age, TREM2-IPD mice had more Tmem119-positive microglia and a greater percentage of proliferating microglia than mice expressing wild-type Trem2. Unknown. Levels of soluble TREM2 were decreased and levels of cell-surface TREM2 were increased in TREM2-IPD mice, compared with wild-type. The IPD mutation accelerated microglial maturation and increased microglial phagocytic activity. Available from Novartis Pharma AG under an MTA. Contact Ivan Galimberti (ivan.galimberti@novartis.com) or Derya Shimshek (derya.shimshek@novartis.com). Dhandapani et al., 2022, Beckmann et al., 2023 Yes
<p>-</p>, <p>TREM2-IPDxAPP23xPS45</p>, <p>APP23xPS45xIPD</p> C57BL/6 Trem2, APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 G384A Trem2-IPDxAPP23xPS45 mice have a modified murine Trem2 gene (resulting in disruption of the ADAM protease cleavage site after amino acid 157) and carry transgenes for human APP and PSEN1 with the AD-linked Swedish and G384A mutations, respectively. Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, plaque-associated neuritic dystrophies, microgliosis. Pathology exacerbated in Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 mice expressing wild-type Trem2, at an early—but not late—stage of plaque deposition. Unknown. Microglial maturation accelerated in Trem2-IPDxAPP23xPS45  mice, compared with APP23xPS45 mice expressing wild-type Trem2. TREM2-IPD and PS45 mice are available from Novartis Pharma AG under an MTA. Contact Ivan Galimberti (ivan.galimberti@novartis.com) or Derya Shimshek (derya.shimshek@novartis.com). APP23 mice are available through The Jackson Laboratory Stock# 030504, Live. Dhandapani et al., 2022 Yes
<p>-</p>, <p>Trem2<sup>-/-</sup> (Colonna)</p> C57BL/6 -TREM2tm1cln C57BL/6 Trem2 Inactivation of the mouse Trem2 gene by targeted deletion of exons 3 and 4 Trem2: Knock-Out Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease Microglial number remains constant and microglial size decreases with age in the corpus callosum of Trem2 KO mice, while microglial number increases and microglial size remains stable in wild-type mice. No cognitive/behaviorial deficits observed. Osteopenic. Impaired microglial response to experimental demyelination, middle cerebral artery occlusion, and facial nerve axotomy. Available through Marco Colonna Turnbull et al., 2006 Yes
<p>-</p>, <p>Trem2<sup>-/-</sup>5XFAD</p>, <p>mTrem2<sup>-/-</sup>5XFAD</p><p>&nbsp;</p> C57BL/6 -TREM2tm1cln; B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmja C57BL/6 Trem2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 5XFAD mice were crossed with Trem2 KO mice. TREM2 KO: Targeted deletion of exons 3 and 4 of mouse Trem2. 5XFAD express two transgenes: 1) human APP with the Swedish, Florida and London mutations, containing the 5' untranslated region and driven by the mouse Thy1 promoter and 2) human PSEN1 with the M146L and L286V mutations driven by the mouse Thy1 promoter. Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes. No data. Trem2 KO: available through Marco Colonna. 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Wang et al., 2015 Yes
<p>-</p>, <p>Trem2<sup>-/-</sup>PS19</p> C57BL/6 -TREM2tm1cln; B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J C57BL/6 Trem2, MAPT MAPT P301S Trem2 KO (Colonna) mice were crossed with PS19 mice. TREM2 KO: Inactivation of the mouse Trem2 gene was achieved by targeted deletion of exons 3 and 4. PS19: express human MAPT (1N4R) with the P301S mutation, driven by the mouse prion protein (Prnp) promoter. Trem2: Knock-Out; MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Microgliosis, astrogliosis, and brain atrophy in Trem2-/-PS19 mice are greatly attenuated compared with Trem2+/+PS19 animals. No data. Trem2 KO: available through Marco Colonna. PS19: The Jackson Lab: Stock# 008169; Live Leyns et al., 2017 Yes
C57BL/6J-Trem2em2Adiuj/J C57BL/6J Trem2 Trem2 expression was ablated using CRISPR/Cas9. Non-homologous end joining resulted in a 175-bp deletion that introduced a stop codon at amino acid 17. Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease No data.. No data. The Jackson Lab: Stock# 027197; Live The Jackson Laboratory Yes
<p>-</p>, <p>Trem2 −/− (KOMP)</p> Trem2tm1(KOMP)Vlcg C57BL/6N Trem2 The entire coding region of the Trem2 gene was replaced by Velocigene cassette ZEN-Ub1 (lacZ -p(A)-loxP-hUbCpro-neor-p(A)-loxP). Trem2: Knock-Out Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease No data. At six months, mice perform normally in the open-field test, elevated plus maze, three-chamber social-interaction test, and contextual and cued fear-conditioning test. Trem2−/− microglia show a muted response to excitotoxicity in vivo, and decreased proliferation and increased apoptosis in vitro. Overexpression of Treml1 is driven by an ectopic Ubiquitin C promoter in the selection cassette. UC Davis KOMP Repository, Project VG10093, cryo-recovery or sperm Kang et al., 2018 Yes
<p>-</p>, <p>APPPS1;Trem2<sup>-/-</sup></p> TREM2tm1(KOMP)Vlcg; B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr C57BL/6 Trem2, APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 L166P Trem2-/-: The entire coding region of the Trem2 gene was replaced by Velocigene cassette ZEN-Ub1 (lacZ-p(A)-loxP-hUbCpro-neor-p(A)-LoxP). APPPS1: Mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter. Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Reduced plaque burden at early stages of plaque deposition but increased plaque burden at later stages, fewer plaque-associated myeloid cells and astrocytes, less phospho-tau in plaque-associated dystrophic neurites, compared with APPPS1. No data. APPPS1 available through Mathias Jucker; Trem2 KO available through UC Davis KOMP Repository, Project VG10093, cryo-recovery or sperm Jay et al., 2015, Jay et al., 2017 Yes
<p>-</p>, <p>hTau;Trem2<sup>−/−</sup></p> TREM2tm1(KOMP)Vlcg; B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J C57BL/6 Mapt, MAPT, Trem2 Htau mice were bred to Trem2−/− mice (Trem2tm1(KOMP)Vlcg) to generate hTau;Trem2−/− and htau/Trem2+/+ mice. These mice were backcrossed for four generations, and maintained on a C57BL/6 background. Mapt: Knock-Out; MAPT: Transgenic; Trem2: Knock-Out Nasu-Hakola Disease, Alzheimer's Disease, Frontotemporal Dementia Tau phosphorylation and aggregation in the cortex are enhanced in htau mice lacking TREM2, but reactive microglia are smaller and their processes have fewer branches. No data. Levels of stress-related protein kinases are elevated in the cortices and hippocampi of hTau;Trem2−/− compared with htau;Trem2+/+ mice. htau: The Jackson Lab: Stock# 005491, live; research services with this line available from the CRO Scantox Neuro. Trem2 KO: UC Davis KOMP Repository, Project VG10093, cryorecovery or sperm. Bemiller et al., 2017 Yes
<p>-</p>, <p>TREM2 Reporter Mouse</p> B6J-Trem2em4(mKate2)Bwef C57Bl/6J CRISPR/Cas9 gene editing was used to insert the reporter construct into the mouse Trem2 locus, immediately downstream of exon 5. This construct contained a P2A (peptide 2A) sequence followed by mKate2 with the KDEL endoplasmic reticulum-retention sequence fused to its C terminus. Silent mutations were also introduced into Trem2 to aid in genotyping. Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease Unknown. Unknown. Bicistronic expression of endogenous Trem2 and the fluorescent protein mKate2 under control of the endogenous Trem2 promoter. Available through Christian Haass. Feiten et al. No
<p>-</p>, <p>Trem2*R47H<sup>HSS</sup></p> B6.Cg-Trem2em4Adiuj/J C57BL/6J Trem2 TREM2 R47H CRISPR/Cas9 was used to edit the mouse Trem2 locus in the Trem2 R47H KI (JAX) model (JAX #27918), “humanizing” the cryptic splice acceptor site in exon 2 in the context of the existing R47H point mutation and two silent mutations. Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. Register interest at The Jackson Laboratory, Stock No. 033781. The Jackson Laboratory Yes
<p>-</p>, <p>R47H ki</p> Trem2em2 Bwef C57BL/6N Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce an R47H point mutation (arginine CGC > histidine CAC) and three silent mutations (glycine: GGG > GGT; arginine: AGA > CGA; lysine: AAG > AAA) into the mouse Trem2 gene. The silent mutations were added to aid in genotyping and increase the efficiency of gene editing. Trem2: Knock-In Alzheimer's Disease Unknown. Unknown. R47H KI mice exhibit a gene-dose-dependent reduction in expression of Trem2, due to aberrant splicing of the mutant allele. Available through Christian Haass. Xiang et al., 2018 Yes
<p>-</p>, <p>MODEL-AD R47H</p>, <p>Trem2*R47H<sup>CSS</sup> (for cryptic splice site)</p>, <p>B6.Trem2*R47H</p> C57BL/6J-Trem2em1Adiuj/J C57BL/6J Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce an R47H missense mutation and two silent mutations—to aid in genotyping and increase gene-editing efficiency—into the mouse Trem2 gene. Trem2: Knock-In Alzheimer's Disease No neuron loss, amyloid plaques, or neurofibrillary tangles were observed in mice up to 24 months of age. Locomotor activity, motor coordination, and working memory similar to wild-type at 2 and 12 months of age. Compared with wild-type mice: age-, sex-, and region-dependent differences in glucose uptake and cerebral blood flow; increased mortality of females at 24 months of age; downregulation of genes related to immune function, and degradation of biological material in aged mice. The Jackson Lab:Stock# 027918; Cryorecovery. Kotredes et al., 2021, Tran et al., 2023 Yes
<p>-</p>, <p>Trem2<sup>+/R47H</sup></p> C57BL6/J Trem2 TREM2 R47H CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene. Trem2: Knock-In Alzheimer's Disease No 6E10- or Thioflavin S-positive amyloid plaques were observed at 4 months of age. Unknown. Approximate 40 percent decrease in levels of Trem2 mRNA in cortices of Trem2+/R47H mice compared with Trem2+/+ mice. Available through Gary Landreth or Bruce Lamb. Cheng-Hathaway et al., 2018 Yes
<p>-</p>, <p>APPPS1-21;Trem2<sup>+/R47H</sup></p> C57BL6/J Trem2, APP, PSEN1 TREM2 R47H, APP K670_M671delinsNL (Swedish), PSEN1 L166P To create Trem2+/R47H mice, CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene. APPPS1-21 mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter. Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, fewer plaque-associated myeloid cells, and worse plaque-associated neuritic dystrophy, compared with APPPS1-21 mice homozygous for wild-type Trem2. Unknown. Levels of Trem2 transcripts were reduced in APPPS1-21;Trem2+/R47H compared with APPPS1-21;Trem2+/+ and were similar to those in APPPS1-21 mice haploinsufficient for Trem2. Trem2+/R47H available through Gary Landreth or Bruce Lamb; APPPS1-21 available through Mathias Jucker. Cheng-Hathaway et al., 2018 Yes
<p>LOAD1</p>, <p>APOE4/Trem2*R47H</p>, <p>APOE*4/Trem2*R47H</p>, <p>APOE4.Trem2*R47H</p> B6(SJL)-Apoetm1.1(APOE*4)Adiuj Trem2em1Adiuj/J C57BL/6J APOE, Trem2 TREM2 R47H, APOE C130R (ApoE4) This double-mutant line was generated by crossing APOE4 KI mice (Jackson Lab Stock# 027894), which carry a humanized APOE4 gene, to Trem2 R47H KI mice (Jackson Lab Stock # 027918), which have an R47H missense mutation knocked into the mouse Trem2 gene. APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease No neuron loss, amyloid plaques, neurofibrillary tangles, vascular leakage, myelin loss, or reactive microglia in mice up to 24 months of age. Age-related changes in locomotor activity, motor coordination, and working memory, but no genotype-dependent differences through 24 months of age, compared with wild-type mice. Age-, sex-, and region-dependent differences in glucose uptake and cerebral blood flow, compared with wild-type mice. Increased mortality at 24 months of age. Down-regulation of genes related to immune function and degradation of biological material in aged mice. The Jackson Lab:Stock# 028709; Live Kotredes et al., 2021 Yes
<p>-</p>, <p>Trem2*R47H<sup>NSS</sup></p> B6(SJL)-Trem2em1Aduci/J C57BL/6J Trem2 TREM2 R47H CRISPR/Cas9 was used to edit the mouse Trem2 gene, introducing the R47H point mutation and 10 silent mutations in exon 2. Trem2: Knock-In Alzheimer's Disease Changes in microglial morphology at 4 months but not 12 months, compared with wild-type. Unknown. Age-dependent synaptic deficits and age-dependent differences in gene expression, compared with wild-type mice. When crossed with 5xFAD mice, blunted inflammatory responses at 4 months, but exaggerated responses at 12 months. Available from The Jackson Laboratory, Stock No. 034036. Tran et al., 2023, The Jackson Laboratory Yes
<p>-</p>, <p>Segmentally trisomic Ts(17<sup>16</sup>)65Dn</p>, <p>Down Syndrome-segmental trisomy 16</p> B6EiC3Sn a/A-Ts(1716)65Dn/J DBA/2J Cesium irradiation produced a reciprocal translocation of chromosomes 16 and 17, creating a freely segregating, supernumerary chromosome Mmu1716 (1716). Other Alzheimer's Disease, Down's Syndrome Brain is grossly normal. Age-dependent cholinergic neurodegeneration and reduced NGF in the basal forebrain. Age-related elevation of APP and Aβ in the hippocampus but no β-amyloid pathology. Early developmental delay. Deficits in behavioral and cognitive tasks including spatial learning and memory deficits as assessed by the Morris water maze and the radial arm maze. Developmental delay in sensorimotor milestones. Locomotor hyperactivity. Lack of behavioral inhibition. Stereotypic behavior. Females are smaller, and produce fewer, smaller litters. Males are effectively sterile with hypospermia. The Jackson Lab: Stock# 001924; Live. The CRO PsychoGenics offers research services with this line. Davisson et al., 1990 No
WSB.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How WSB/EiJ APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with WSB/EiJ mice for at least six generations. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in cortex and hippocampal area CA1 in females. Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in females (data from males is not available, as wild-type males are unable to perform this test). Available from The Jackson Laboratory, Stock #25970. Onos et al., 2019 Yes
Rat Models (19)
<p>-</p>, <p>AgenT</p> Wistar APP, PSEN1 APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M146L (A>C) Adeno-associated viral vectors separately encoding human APP with the Swedish and London mutations and human PSEN1 with the M146L mutation were injected bilaterally into the hippocampi of young adult (8-week-old) rats. APP: Virus; PSEN1: Virus Alzheimer's Disease Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection. Anti-phospho-tau immunostaining suggests the presence of (pre)tangle-like structures. No astrogliosis seen up to 30 months post-injection. Compared with control rats at 8 months post-injection, AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training and less time in the center of the open field. At 8 months post-injection, long-term potentiation was impaired in hippocampal slices obtained from AAV-AD rats, compared with controls, but the groups did not differ with regards to long-term depression. Viral vectors are available through AgenT SAS under collaboration or partnership agreements. Audrain et al., 2017 Yes
F344-Tg(APP)21Besey Fischer 344 APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) A lentiviral vector carrying a human APP695 transgene was injected into Fischer 344 zygotes. This transgene contains the Swedish and Indiana mutations and is driven by the ubiquitin-C promoter. APP: Transgenic Alzheimer's Disease No plaques to 30 months of age. Necrotic neurons in hippocampus and cortex by 19 months, in females; neuron loss not observed in cortices of 19-month males. Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age. Available from the Rat Resource & Research Center, Stock# 00636; cryorecovery, sperm Agca et al., 2008 Yes
<p>-</p>, <p>App<sup>h</sup></p>, <p>App<sup>h/h</sup></p> Long-Evans App Three point mutations were introduced into the rat App gene to humanize the Aβ sequence (G5R, F10Y, and R13H of Aβ). App: Knock-In Alzheimer's Disease No plaques, neurofibrillary tangles, or neuron loss observed at three months, the oldest age reported. Unknown. Available through Luciano D'Adamio. Tambini et al., 2019 Yes
<p>-</p>, <p>App<sup>hu/hu</sup></p> Long Evans App CRISPR/Cas9 was used to introduce the following mutations into the endogenous App gene: G676R (G5R), F681Y (F10Y), R684H (R13H), numbered according to the 770 amino-acid isoform of human APP (position within the Aβ sequence). App: Knock-In Alzheimer's Disease No plaques or tangles were observed up to two years of age. Unknown. Levels of CTFβ and Aβ are elevated in the brains of these knock-in rats, compared with wild-type animals. Available through Lutgarde Serneels. Serneels et al., 2020 Yes
<p>-</p>, <p>App<sup>hu/hu</sup>;Psen1M139T<sup>+/+</sup></p> Long Evans App, Psen1 PSEN1 M139T Crispr/Cas9 was used to humanize the Aβ sequence within the rat App gene and to introduce the M139T mutation into the rat Psen1 gene. App: Knock-In; Psen1: Knock-In Alzheimer's Disease No plaques or tangles were observed up to 2 years of age. Unknown. Elevated levels of CTFβ and Aβ compared with wild-type rats. Increased Aβ42/Aβ40 ratio relative to rats homozygous for humanized App, but without the Psen1 mutation. Available through Lutgarde Serneels. Serneels et al., 2020 Yes
<p>-</p>, <p>App<sup>p</sup></p> Long-Evans App APP A673T (Icelandic) Four point mutations were introduced into the rat App gene to humanize the Aβ sequence (G5R, F10Y, and R13H of Aβ) and to add the Icelandic mutation A673T (numbered as in the 770-amino-acid isoform of human APP). App: Knock-In Alzheimer's Disease Unknown. Unknown. Available through Luciano D'Adamio. Tambini et al., 2020 Yes
<p>-</p>, <p>App<sup>s</sup></p> Long-Evans App APP K670_M671delinsNL (Swedish) Five point mutations were introduced into the rat App gene to humanize the Aβ sequence (G5R, F10Y, and R13H of Aβ) and to add the AD-linked Swedish double mutation, KM670/671NL (numbered as in the 770-amino-acid isoform of human APP). App: Knock-In Alzheimer's Disease No plaques, neurofibrillary tangles, or neuron loss observed at 3 months, the oldest age reported. Unknown. Increased amplitude and decreased frequency of miniature excitatory postsynaptic currents; deficits in paired-pulse facilitation at excitatory synapses. Available through Luciano D'Adamio. Tambini et al., 2019, Tambini et al., 2020 Yes
<p>-</p>, <p>App<sup>NL-G-F</sup> rat</p>, <p>APP Swe-Arc-Ibe knock-in rat</p> Sprague Dawley App APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP I716F (Iberian) This rat line, created using CRISPR/Cas9 technology, carries a humanized Aβ sequence (G676R, F681Y, and R684H) and three AD-linked mutations (Swedish, KM670/671NL; Arctic, E693G; and Iberian, I716F) in the endogenous rat App gene. App: Knock-In Alzheimer's Disease Amyloid plaques apparent as early as 1 month in homozygous knock-ins. No neurofibrillary tangles through 22 months of age, but increases in tau phosphorylation, aggregation, and conformational changes. Astrogliosis, microgliosis, synapse and neuron loss. Deficits in the Morris Water Maze task and a paired associate learning task as early as 5 and 7 months of age, respectively. Available through Bai Lu. Pang et al., 2022 Yes
Fischer 344 APP, PSEN1 APP K670_M671delinsNL (Swedish), APP V717F (Indiana), PSEN1 L166P APP+PS1 transgenic rats express human APP with the Swedish and Indiana mutations and human PSEN1 with the L166P mutation. Both transgenes are driven by the ubiquitin-C promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age. Deficits in Barnes maze by 10 months of age. Unknown. Agca et al., 2016, Klakotskaia et al., 2018 Yes
<p>Cy23</p> Sprague-Dawley Mapt These tau knockout rats were created through transcription activator-like effector nuclease (TALEN)-mediated targeting of exon 2 of the rat Mapt gene. Mapt: Knock-Out Alzheimer's Disease None reported. Unknown. No gross phenotypes reported. Contact David Westaway, Institute for Neurodegenerative Diseases, UCSF. Ayers et al., 2024 No
HsdBrl:WH Wistar APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) Transgene contains entire coding region of human APP751 with the Swedish and Indiana mutations and approximately 900 bp of 3' non-translated sequence, driven by the murine Thy1.2 promoter. APP: Transgenic Alzheimer's Disease Hemizygotes: intraneuronal Aβ in hippocampus and cortex by one week, but no plaques even at advanced ages. Homozygotes: intraneuronal Aβ in hippocampus and cortex by one week; amyloid plaques in hippocampus beginning at 6 months, in cortex beginning at 13 months. Cognitive deficits are apparent by three months of age in both hemizygous and homozygous transgenic rats. Resting-state fMRI showed disrupted cingulate network connectivity by 9 to11 months; FDG-PET showed hypometabolism by 16 to 19 months (homozygotes). Breeding pairs available via a royalty agreement with McGill University; contact Adriana Ducatenzeiler. Leon et al., 2010 Yes
<p>-</p>, <p>Psen1<sup>LF</sup></p> Long-Evans Psen1, App PSEN1 L435F Rats carry a mutation in the endogenous Psen1 gene that is homologous to the human L435F mutation, as well as a humanized Aβ sequence within the endogenous App gene. Psen1: Knock-In; App: Knock-In Alzheimer's Disease None observed in 15-day-old rats. Unknown. Levels of Aβ43 are elevated in the brains of homozygous and heterozygous Psen1 mutation carriers. Available through Luciano D’Adamio. Tambini and D'Adamio, 2020 Yes
SHR MAPT SHR24 rats express a gene encoding amino acids 151-274 and 306-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R). MAPT: Transgenic Alzheimer's Disease Neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem, beginning at 9 to 10 months. No neuron loss was observed in the hippocampus or cortex. SHR24 rats exhibit age-dependent impairments in several neurobehavioral tests; hind-limb clasping during the tail-hang test is one of the earliest abnormalities to appear, evident by 3.5 months of age. SHR24 rats have a shorter lifespan (approximately 14 months) than wild-type SHR rats (22-24 months). Unknown. Filipcik et al., 2012, Valachova et al., 2018 Yes
SHR MAPT SHR318 rats express a gene encoding amino acids 151-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R). MAPT: Transgenic Alzheimer's Disease Neurofibrillary tangles first appear at 9 months and are particularly prominent in the brainstem and spinal cord. Axonal degeneration is observed in the brainstem and spinal cord of 10- to 12-month animals. At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze. Reflexes and sensorimotor coordination are impaired at 7 months. SHR72 rats have a shorter lifespan (approximately 10–12 months) than wild-type SHR rats (22–24 months). No longer available. Zilka et al., 2006, Hrnkova et al., 2007 Yes
SHR MAPT SHR72 rats express a gene encoding amino acids 151-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R). MAPT: Transgenic Alzheimer's Disease Neurofibrillary tangles, demonstrated by Gallyas silver stain, were found the brainstems and spinal cords of terminal stage (7- to 8-month old) animals. Chromatolytic neurons and damaged axons were also observed at this stage. Sensorimotor deficits and loss of muscle strength are apparent at 3 months. This stage lasted about three months, and then rats experienced a rapid, dramatic decline in neurological function, succumbing within several days. SHR72 rats have a shorter lifespan (approximately 7-8 months) than wild-type SHR rats (22-24 months). Unknown. Koson et al., 2008 Yes
Spontaneously hypertensive stroke-prone (SHRSP); Fischer 344 APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 TgF344-AD rats, which carry human APP and PSEN1 transgenes, with the AD-linked Swedish and Δ exon 9 mutations, respectively, were backcrossed with spontaneously-hypertensive-stroke-prone (SHRSP) rats. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease, Vascular Dementia Amyloid plaques, microgliosis, and possible astrogliosis. Occasional neurons appear to contain paired helical filament tau. Demyelination. Reduced calbindin immunoreactivity and increased levels of caspase-cleaved actin may indicate neuron loss. Hyperactive. Working memory deficits as assessed by novel object recognition, but not as assessed by spontaneous alternation in the Y-maze. Hypertensive. Available through Sally Frautschy. Denver et al., 2019 Yes
Sprague-Dawley MAPT MAPT P301S Tg12099 rats express the 0N4R isoform of human MAPT with P301S mutation linked to frontotemporal dementia, driven by the rat Prnp promoter. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Tau pathology, including neurofibrillary tangles, forebrain neurodegeneration, and astrogliosis in homozygotes. Hemizygotes exhibit little pathology, save for a few AT8-immunoreactive neurons in the entorhinal cortices of aged animals. Ataxia, bradykinesia, and seizures reported in aging homozygotes. Premature death of homozygotes, with median survival of 14 months. Contact David Westaway, Institute for Neurodegenerative Diseases, UCSF. Ayers et al., 2024 Yes
Fischer 344 APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 TgF344-AD rats express human APP with the Swedish mutation and human PSEN1 with the Δ exon 9 mutation. Both transgenes are driven by the mouse prion promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, microgliosis, and astrogliosis by 6 months. Neurofibrillary tangle-like structures at 16 months. Approximate 40 percent loss of neurons in hippocampus and cortex by 16 months. Earliest reported deficits are in reversal learning in the Morris water maze, apparent by 6 months. Available through Terrence Town. Cohen et al., 2013 Yes
<p>-</p>, <p>Trem2<sup>R47H</sup></p> Long-Evans Trem2, App TREM2 R47H Rats carry the R47H mutation in the endogenous Trem2 gene and a humanized Aβ sequence within the endogenous App gene. Trem2: Knock-In; App: Knock-In Alzheimer's Disease Unknown. Unknown. Available through Luciano D'Adamio. Tambini and D'Adamio, 2020 Yes

175 Visualizations

Phenotypes Examined

  • Plaques
  • Tangles
  • Neuronal Loss
  • Gliosis
  • Synaptic Loss
  • Changes in LTP/LTD
  • Cognitive Impairment

When visualized, these phenotypes will distributed over a 18 month timeline demarcated at the following intervals: 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.

3xTg

Observed
  1. X
    Plaques at 26

    Extracellular Aβ deposits by 6 months in the frontal cortex, predominantly layers 4 and 5 and progress with age (Oddo et al., 2003).

  2. X
    Tangles at 52

    By 12 months extensive tau immunoreactivity in CA1 neurons of the hippocampus, particularly pyramidal neurons, later in the cortex. No tau pathology at 6 months (Oddo et al., 2003).

  3. X
    Gliosis at 30

    Increased density of GFAP immunoreactive astrocytes and IBA-1 immunoreactive microglia compared with wild-type mice at 7 months (Caruso et al., 2013). Development of gliosis may occur earlier.

  4. X
    Changes in LTP/LTD at 26

    By 6 months decreased LTP compared with wild type controls. Impairment in basal synaptic transmission. No change at 1 month of age (Oddo et al., 2003).

  5. X
    Cognitive Impairment at 17

    Cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Aβ in the hippocampus and amygdala, but plaques and tangles are not yet apparent (Billings et al., 2005).

Absent
No Data
  • Neuronal Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Psen1, APP, MAPT APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic Alzheimer's Disease

Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles.

Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task.

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5xFAD (B6SJL)

Observed
  1. X
    Plaques at 8

    Extracellular amyloid deposition begins around 2 months, first in the subiculum and layer V of the cortex. Aβ42 also accumulates intraneuronally in an aggregated form within the soma and neurites starting at 1.5 months.

  2. X
    Neuronal Loss at 24

    Neuron loss in cortical layer V and subiculum.

  3. X
    Gliosis at 8

    Gliosis begins at 2 months.

  4. X
    Synaptic Loss at 16

    Levels of the presynaptic marker synaptophysin begin to decline by 4 months; levels of syntaxin, another presynaptic marker, and PSD-95, a postsynaptic marker, decline by 9 months

  5. X
    Changes in LTP/LTD at 24

    Basal synaptic transmission and LTP in hippocampal area CA1 begin to deteriorate between 4 and 6 months

  6. X
    Cognitive Impairment at 18

    Impaired spatial working memory in the Y-maze test and impaired remote memory stabilization in a contextual-fear-conditioning test by 4 to 5 months of age.

Absent
  • Tangles at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles.

Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype.

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5xFAD (C57BL6)

Observed
  1. X
    Plaques at 8

    Amyloid plaques observed in hippocampus, cortex, thalamus, and spinal cord.

  2. X
    Neuronal Loss at 52

    Approximate 40 percent loss of layer V pyramidal neurons at one year.

  3. X
    Gliosis at 8

    Microgliosis and astrogliosis are associated with amyloid plaques; microgliosis is associated with vascular damage.

  4. X
    Synaptic Loss at 24

    Spine density was reduced in pyramidal neurons in somatosensory and prefrontal cortices, but not in the hippocampi, of 5xFAD mice crossed with mice expressing yellow fluorescent protein (YFP mice), compared with mice expressing YFP alone.

  5. X
    Changes in LTP/LTD at 8

    While spike-timing-dependent long-term potentiation was induced in layer V neurons from wild-type mice, the same stimulation protocol induced long-term depression in neurons from 5xFAD mice.

  6. X
    Cognitive Impairment at 24

    Impairments of spatial working memory and reduced anxiety emerge between 3 and 6 months and worsen with age.

Absent
No Data
  • Tangles at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer V.

Age-dependent memory deficits, motor phenotype, and reduced anxiety.

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A7 APP transgenic

Observed
  1. X
    Plaques at 39

    These mice develop progressive amyloid deposition in the cerebral cortex by 9-12 months. By 21 months of age amyloid pathology is extensive.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP T714I (Austrian) APP: Transgenic Alzheimer's Disease

Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months.

Unknown.

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AAV-AD

Observed
  1. X
    Plaques at 128

    Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection.

  2. X
    Changes in LTP/LTD at 40

    Deficits in LTP as Schaffer collateral-CA1 synapse at 10 months (8 months post-injection).  LTD similar to controls.

  3. X
    Cognitive Impairment at 40

    AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training.

Absent
  • Gliosis at

    No astrogliosis observed up to 30 months post-injection.

No Data
  • Tangles at

    Immunostaining with monoclonal antibodies AT8 and AT100 suggests the presence of (pre)tangle-like structures 30 months post-injection.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M146L (A>C) APP: Virus; PSEN1: Virus Alzheimer's Disease

Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection. Anti-phospho-tau immunostaining suggests the presence of (pre)tangle-like structures. No astrogliosis seen up to 30 months post-injection.

Compared with control rats at 8 months post-injection, AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training and less time in the center of the open field.

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AAV-sTREM2 5xFAD

Observed
  1. X
    Plaques at 28

    When examined at 7 months of age, amyloid plaque burdens in the hippocampus and cortex of AAV-sTREM2 5xFAD mice were about half those of 5xFAD mice injected with control vector.

  2. X
    Gliosis at 28

    The number of plaque-associated microglia was increased in AAV-sTREM2 5xFAD mice examined at 7 months of age.

  3. X
    Changes in LTP/LTD at 24

    Long-term potentiation at Shaeffer collateral-CA1 synapses is impaired in 5xFAD mice. AAV-mediated over expression of sTREM2 rescued LTP in AAV-sTREM2 5xFAD mice.

  4. X
    Cognitive Impairment at 24

    5xFAD mice show impaired learning and memory in the Morris water maze, but AAV-sTREM2 5xFAD mice performed as well as non-transgenic controls.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
TREM2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V TREM2: Virus; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

AAV-mediated over expression of sTREM2 decreased amyloid plaque burdens and increased numbers of plaque-associated microglia in the brains of 5xFAD mice.

5xFAD mice show impaired learning and memory in the Morris water maze, but AAV-sTREM2 5xFAD mice performed as well as non-transgenic controls.

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AAV-sTREM2 PS19

Observed
  1. X
    Synaptic Loss at 28

    AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.

  2. X
    Changes in LTP/LTD at 29

    LTP at Shaeffer collateral-CA1 synapses was slightly enhanced in hippocampal slices from 7-month-old AAV-sTREM2 PS19 mice, compared with PS19 mice who had received control vector.

  3. X
    Cognitive Impairment at 30

    AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze.

Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
TREM2, MAPT MAPT P301S TREM2: Virus; MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.

AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze.

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Abca7*A1527G/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Abca7, APOE, Trem2 TREM2 R47H Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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Abca7 KO/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Abca7, APOE, Trem2 TREM2 R47H Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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ADanPP

Observed
  1. X
    Plaques at 9

    Vascular amyloid deposits and punctate parenchymal aggregates first occur in the hippocampus and increase with age, spreading throughout the brain, including the cortex, amygdala, thalamus, and brainstem in hemizygous mice.

  2. X
    Gliosis at 17

    Astrogliosis and microgliosis increase with age and increasing ADan-amyloid deposition.

  3. X
    Cognitive Impairment at 78

    The only ages tested were 6 months and 18-20 months. Mice 18-20 months of age exhibited both motor and spatial learning defects in the Morris water maze, and increased anxiety in the open field test. No impairments were observed in 6 month-old mice.

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
ITM2B (BRI2) BRI2: Familial Danish Dementia (FDD) duplication ITM2B (BRI2): Transgenic Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy

ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present.

Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype.

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AD-BXD

Observed
  1. X
    Plaques at 24

    Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, the earliest age examined. The extent of plaque deposition is strain-dependent.

  2. X
    Gliosis at 25

    Strain-dependent gliosis by 6 months. 

  3. X
    Cognitive Impairment at 60

    In the AD-BXD population as a whole, transgenic mice performed similarly to non-transgenic littermates in a contextual fear-conditioning test at 6 months, but were impaired at 14 months. The age of onset and severity of impairment are strain-dependent.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, although the extent of plaque deposition is strain-dependent.

Transgenic AD-BXD mice exhibit cognitive deficits, assessed using contextual fear conditioning. The age of onset and severity of impairment are strain-dependent.

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APOE2 Knock-In, floxed (CureAlz)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE2 Knock-In (JAX)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE3 Knock-In, floxed (CureAlz)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE3 Knock-In (JAX)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

No data.

No data.

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APOE3 Knock-In (Lamb)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury

Unknown.

Unknown.

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APOE4 Knock-In, floxed (CureAlz)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APOE4 Knock-In (JAX)

Observed
Absent
  • Cognitive Impairment at

    At 2 and 12 months of age, APOE4 KI mice perform similarly to wild-type mice in tests of locomotor activity, motor coordination, and working memory.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE APOE: Knock-In Alzheimer's Disease

No data.

No data.

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APP21

Observed
  1. X
    Neuronal Loss at 76

    Necrotic neurons in hippocampus and cortex of female rats.

  2. X
    Gliosis at 64

    Activated (MHCII-positive) microglia present in white matter tracts at 15 months.

  3. X
    Cognitive Impairment at 12

    Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.

Absent
  • Plaques at

    Do not spontaneously develop amyloid pathology, but can serve as hosts for exogenously seeded amyloid deposits.

No Data
  • Tangles at

    “Flame-shaped” profiles in hippocampal neurons of 18- to 19-month-old female rats revealed by hematoxylin-and-eosin-staining.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

No plaques to 30 months of age. Necrotic neurons in hippocampus and cortex by 19 months, in females; neuron loss not observed in cortices of 19-month males.

Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.

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APP23

Observed
  1. X
    Plaques at 26

    Congophillic, dense-core amyloid plaques first appear at 6 months, and increase in size and number with age. Amyloid plaques can occupy more than 25% of the neocortex and hippocampus in 24 month-old mice (Sturchler-Pierrat et al., 1997; Calhoun et al., 1998).   

  2. X
    Neuronal Loss at 61

    Neuronal loss (14-28%) has been reported in the CA1 region of the hippocampus in 14-18 month old mice (Calhoun et al., 1998).     

  3. X
    Gliosis at 26

    Activated microglia in close proximity to dense amyloid plaques (Stalder et al., 1999). Upregulation of neuroinflammatory markers and activation of astrocytes and macrophages. Age-associated increase in components of the complement system, namely C1q and C3, at later ages (9 and 18 months, respectively) (Reichwald et al., 2009). 

  4. X
    Cognitive Impairment at 13

    Spatial memory defects in Morris Water maze at 3 months and progresses with age (Van dam et al., 2003; Kelly et al., 2003).

Absent
  • Tangles at

    Dystrophic neurites containing hyperphopshorylated tau surounds Aβ plaques, but no neurofibrillary tangles are observed (Sturchler-Pierrat et al., 1997).

  • Synaptic Loss at

    Neocortical synapses were examined in mice as old as 24 months of age; no evidence of alterations in the number of synapses or levels of synaptophysin were observed (Boncristiano et al., 2005).

  • Changes in LTP/LTD at

    LTP in the hippocampus and prefrontal cortex is normal at all ages studied: 3, 6, 9, 12, 18 and 24 months (Roder at al., 2003).

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages.

Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages.

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APP23 x PS1-R278I

Observed
  1. X
    Plaques at 26

    By 6 months of age amyloid plaques accumulate in the cortex and hippocampus. A high percentage of plaques are thioflavin-S –positive cored plaques.

  2. X
    Gliosis at 39

    Astrocytosis in the vicinity of plaques in the hippocampus and cortex by 9 months.

  3. X
    Cognitive Impairment at 13

    Short-term memory deficits are apparent by 3 to 4 months as measured by the Y maze.

Absent
  • Tangles at

    Not observed.

No Data
  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 PSEN1 R278I APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease

Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques.

Short-term memory deficits apparent by 3-4 months as measured by the Y maze.

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APP751SL/PS1 KI

Observed
  1. X
    Plaques at 11

    Aβ deposition at 2.5 months compared to 6 months in APPSL mice. At 6 months, numerous compact Aβ deposits in the cortex, hippocampus, and thalamus, whereas in age-matched APPSL mice only very few deposits restricted mainly to the subiculum and deeper cortical layers. At 10 months, deposits increased in distribution, density, and size in both models (Casas et al., 2004).

  2. X
    Neuronal Loss at 23

    Some cell loss detectable as early as 6 months in female mice. At 10 months extensive neuronal loss (>50%) is present in the CA1/2 hippocampal pyramidal cell layer. SNeuronal loss also occurs in the frontal cortex and cholinergic system (Casas et al., 2004; Christensen et al., 2008; Christensen et al., 2010).

  3. X
    Gliosis at 11

    Astrogliosis occurs in parallel with Aβ deposition, starting around 2.5 months, and in proximity to Aβ-positive neurons (Wirths et al., 2010).

  4. X
    Synaptic Loss at 24

    At 6 months, levels of pre- and post-synaptic markers are reduced (Breyhan et al., 2009).

  5. X
    Changes in LTP/LTD at 28

    At 6 months there is a large reduction of long-term potentiation and disrupted paired pulse facilitation. No deficit at 4 months (Breyhan et al., 2009).

  6. X
    Cognitive Impairment at 27

    Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates (Wirths et al., 2008).

Absent
  • Tangles at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease

Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons.

Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates.

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APPDutch

Observed
  1. X
    Gliosis at 126

    Microgliosis develops after the onset of CAA pathology and is prominent in areas adjacent to amyloid-laden vessels. There is also widespread activation of astrocytes in neocortical regions affected by CAA. These changes have been reported at 29 months of age, although the actual onset of gliosis may occur earlier than has been examined.

Absent
  • Plaques at

    No plaques are observed, but CAA develops at 22-24 months.

  • Tangles at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP E693Q (Dutch) APP: Transgenic Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease

Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed. 

Unknown.

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APP E693Δ-Tg (Osaka)

Observed
  1. X
    Neuronal Loss at 104

    Neuronal loss, as measured by NeuN staining, was observed in the CA3 region of the hippocampus at 24 months of age. Neuronal loss was not detected in the cerebral cortex at this time.

  2. X
    Gliosis at 52

    At 12 months of age, microgliosis is seen in transgenic mice, as measured by the presence of Iba-1 staining in the hippocampus and cortex. Astrocytosis, as measured by GFAP-reactivity, increased starting around 18 months of age in these regions.

  3. X
    Synaptic Loss at 34

    Starting around eight months of age, transgenic mice exhibit a decrease in synaptic density in the CA3 region of the hippocampus as measured by synaptophysin staining.

  4. X
    Changes in LTP/LTD at 35

    By eight months of age, transgenic mice exhibit reduced short term plasticity as measured by paired-pulse facilitation in addition to reduced LTP as elicited by high frequency stimulation to the perforant pathway.

  5. X
    Cognitive Impairment at 36

    By 8 months of age, transgenic mice exhibit memory impairment in the Morris water maze compared to mice expressing equivalent levels of wild-type human APP.

Absent
  • Plaques at

    Extracelluar amyloid plaques are not observed out to 24 months; however, Aβ accumulates within neurons of the hippocampus and cerebral cortex starting around eight months of age.

  • Tangles at

    Overt tangle pathology is not observed out to 24 months of age, but abnormal tau phosphorylation is observed starting around eight months of age.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP E693del (Osaka) APP: Transgenic Alzheimer's Disease

Age-dependent accumulation of Aβ oligomers within hippocampal and cortical neurons, but negligible deposits of extracellular amyloid. Abnormal tau phosphorylation, but no overt tangle pathology. Synaptic loss and gliosis in hippocampus and cerebral cortex. Late neuronal loss in the CA3 region of the hippocampus.

Memory impairment by eight months as measured by the Morris water maze. Specifically, reduced spatial reference memory in the Morris water maze compared to mice expressing comparable levels of wild-type human APP.

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App knock-in (humanized Aβ)

Observed
Absent
  • Plaques at

    None observed at 3 months.

  • Tangles at

    None observed at 3 months.

  • Neuronal Loss at

    None observed at 3 months.

No Data
  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App App: Knock-In Alzheimer's Disease

No plaques, neurofibrillary tangles, or neuron loss observed at three months, the oldest age reported.

Unknown.

expand

App knock-in (humanized Aβ)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App App: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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App knock-in (humanized Aβ) (Leuven)

Observed
Absent
  • Plaques at

    No plaques observed up to 2 years of age.

  • Tangles at

    No tangles observed up to 2 years of age.

No Data
  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App App: Knock-In Alzheimer's Disease

No plaques or tangles were observed up to two years of age.

Unknown.

expand

App knock-in (humanized Aβ) (Leuven); Psen1 knock-in (M139T)

Observed
Absent
  • Plaques at

    No plaques observed up to 2 years of age.

  • Tangles at

    No tangles observed up to 2 years of age.

No Data
  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App, Psen1 PSEN1 M139T App: Knock-In; Psen1: Knock-In Alzheimer's Disease

No plaques or tangles were observed up to 2 years of age.

Unknown.

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App knock‐in (Icelandic mutation and humanized Aβ)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App APP A673T (Icelandic) App: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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App knock‐in (Swedish mutation and humanized Aβ)

Observed
Absent
  • Plaques at

    None observed at 3 months.

  • Tangles at

    None observed at 3 months.

  • Neuronal Loss at

    None observed at 3 months.

No Data
  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App APP K670_M671delinsNL (Swedish) App: Knock-In Alzheimer's Disease

No plaques, neurofibrillary tangles, or neuron loss observed at 3 months, the oldest age reported.

Unknown.

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App KO/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, App, Trem2 TREM2 R47H APOE: Knock-In; App: Knock-Out; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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APP NL-F Knock-in

Observed
  1. X
    Plaques at 26

    Homozygotes develop amyloid plaques starting at 6 months in the cortex and hippocampus. Heterozygotes develop amyloidosis after 24 months. Plaques contained Aβ1-42 and pyroglutamate Aβ (Aβ3(pE)-42); Aβx-40 was a minor species.

  2. X
    Gliosis at 26

    Microglia and activated astrocytes accumulate with age, starting around 6 months of age, concurrent with plaque formation.

  3. X
    Synaptic Loss at 39

    Reduced synaptophysin and PSD95 immunoreactivities associated with Aβ plaques at 9-12 months.

  4. X
    Cognitive Impairment at 78

    Memory impairment in homozygous mice at 18 months as measured by the Y maze test. APPNL/NL mice (with Swedish mutation only) were unimpaired at this age. No significant deficit was seen in the Morris water maze at 18 months.

Absent
  • Tangles at

    Absent; although elevated levels of phosphorylated tau are observed in dystrophic neurites around plaques.

  • Neuronal Loss at

    Absent.

No Data
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP I716F (Iberian) APP: Knock-In Alzheimer's Disease

Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.

Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze.

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APP NL-G-F Knock-in

Observed
  1. X
    Plaques at 9

    Aggressive amyloidosis; plaques develop in homozygous mice starting at 2 months with near saturation by 7 months. Aβ deposition at 4 months in heterozygous mice. Cortical and subcortical amyloidosis present.

  2. X
    Gliosis at 9

    Microglia and activated astrocytes accumulate with age starting around 2 months, especially around plaques in a manner concurrent with plaque formation.

  3. X
    Synaptic Loss at 17

    Reduction of synaptophysin and PSD95 immunoreactivities associated with Aβ plaques in both cortical and hippocampal areas.

  4. X
    Cognitive Impairment at 26

    Memory impairment in homozygous mice by 6 months of age as measured by the Y maze.

Absent
  • Tangles at

    Absent; although phosphorylated tau is elevated in dystrophic neurites around plaques.

  • Neuronal Loss at

    Absent.

No Data
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) APP: Knock-In Alzheimer's Disease

Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.

Memory impairment by 6 months as measured by the Y maze.

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App NL-G-F Knock-in Rat

Observed
  1. X
    Plaques at 4

    Amyloid plaques apparent as early as 1 month in homozygous knock-ins, 4 months in heterozygotes. Amyloid pathology progresses more rapidly in females than males.

  2. X
    Neuronal Loss at 52

    Reduced brain weight, fewer neurons in the hippocampus and cortex, and enlarged lateral ventricles seen at 12 months.

  3. X
    Gliosis at 24

    Astrogliosis and microgliosis, particularly pronounced around amyloid plaques, were observed in homozygous knock-in rats at 6 months of age. Gliosis was also seen in year-old heterozygotes.

  4. X
    Synaptic Loss at 24

    Decreased levels of the presynaptic marker synaptophysin and the postsynaptic marker PSD-95 in knock-in rats. Quantitative electron microscopy showed reductions in synaptic density, area, and perimeters in the hippocampus, entorhinal cortex and prefrontal cortex of knock-in brains.

  5. X
    Cognitive Impairment at 20

    Deficits in the Morris Water Maze task and a paired associate learning task as early as 5 and 7 months of age, respectively.

Absent
  • Tangles at

    No neurofibrillary tangles through 22 months of age, but increases in tau phosphorylation, aggregation, and conformational changes.

No Data
  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP I716F (Iberian) App: Knock-In Alzheimer's Disease

Amyloid plaques apparent as early as 1 month in homozygous knock-ins. No neurofibrillary tangles through 22 months of age, but increases in tau phosphorylation, aggregation, and conformational changes. Astrogliosis, microgliosis, synapse and neuron loss.

Deficits in the Morris Water Maze task and a paired associate learning task as early as 5 and 7 months of age, respectively.

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AppNL-G-F/MAPT double knock-in

Observed
  1. X
    Plaques at 8

    Plaques observed at 2 months.

  2. X
    Gliosis at 16

    Astrogliosis and microgliosis observed by 4 months.

  3. X
    Cognitive Impairment at 52

    Deficits in the Y-maze test of working memory at 12 months of age.

Absent
  • Tangles at

    No neurofibrillary tangles observed up to 24 months of age.

  • Neuronal Loss at

    No neurodegeneration observed up to 24 months of age.

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App, MAPT APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) App: Knock-In; MAPT: Knock-In Alzheimer's Disease

Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to AppNL-G-F.

Deficits in the Y-maze test of working memory, similar to AppNL-G-F.

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APPPS1

Observed
  1. X
    Plaques at 6

    Aβ deposition begins at 6 weeks of age in the cortex and 3-4 months of age in the hippocampus (Radde et al., 2006).

  2. X
    Neuronal Loss at 74

    Global neuron loss is not observed, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuronal density in 17-month old animals (Rupp et al., 2011).

  3. X
    Gliosis at 6

    Activated microglia around Aβ deposits at 6 weeks as well as increased astrogliosis (Radde et al., 2006). Levels of CCL2 and TNFα increase at later ages (Lee et al., 2010).

  4. X
    Synaptic Loss at 10

    Dendritic spine loss around plaques reported to begin approximately 4 weeks after plaque formation and continue for several months (Bittner et al., 2012).

  5. X
    Changes in LTP/LTD at 35

    Hippocampal CA1 LTP normal at 4.5 months of age, but impaired at 8 and 15 months of age (Gengler et al., 2010).

  6. X
    Cognitive Impairment at 30

    Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006).

Absent
  • Tangles at

    Phosphorylated tau-positive neuritic processes around plaques have been observed, but no mature tangles (Radde et al., 2006).

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 L166P APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.

 

Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months.

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APP+PS1

Observed
  1. X
    Plaques at 76

    Abundant plaques in hippocampus and subiculum, scattered plaques in cortex.

  2. X
    Neuronal Loss at 76

    Necrotic neurons in hippocampus and cortex.

  3. X
    Cognitive Impairment at 40

    Deficits in Barnes maze at 10 months.

Absent
No Data
  • Tangles at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), APP V717F (Indiana), PSEN1 L166P APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age.

Deficits in Barnes maze by 10 months of age.

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APP/PS1/rTg21221

Observed
  1. X
    Plaques at 35

    Cortical plaques observed between 8-10 months. Plaques larger than in control mice not expressing human tau.

  2. X
    Neuronal Loss at 36

    Neuronal loss observed adjacent to plaques relative to more distal areas.

  3. X
    Gliosis at 37

    Increased astrocytosis adjacent to plaques relative to more distal areas.

  4. X
    Synaptic Loss at 40

    Decreased synapse density adjacent to plaques relative to more distal areas.

Absent
  • Tangles at

    No tangles. Aggregates of misfolded and phosphorylated tau observed between 8-10 months.

No Data
  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1, MAPT APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic Alzheimer's Disease

Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed.

No data.

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AppSAA Knock-in

Observed
  1. X
    Plaques at 16

    Amyloid plaques seen in AppSAA homozygous mice from 4 months of age and heterozygous mice at 16 months of age.

  2. X
    Gliosis at 16

    Plaque-associated microgliosis observed by 4 months of age.

Absent
  • Tangles at

    AT8-positive dystrophic neurites, but no neurofibrillary tangles, detected in AppSAA homozygous mice at 8 months of age.

No Data
  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP T714I (Austrian) App: Knock-In Alzheimer's Disease

Homozygotes: Amyloid plaques and plaque-associated microgliosis from 4 months of age; cerebral amyloid angiopathy and dystrophic neurites from 8 months of age. Heterozygotes: Amyloid plaques at 16 months of age.

Unknown.

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APPsw/0; Pdgfrβ+/-

Observed
  1. X
    Plaques at 39

    By 9 months of age APPsw/0;Pdgfrβ+/- mice have an elevated plaque load in the cortex and hippocampus compared with age matched APPsw/0;Pdgfrβ+/+. littermates. They also have extensive cerebral amyloid angiopathy.

  2. X
    Neuronal Loss at 39

    Progressive neuronal degeneration including reduced neurite density and reduced neuronal number in the cortex and hippocampus of APPsw/0; Pdgfrβ+/- mice at at nine months compared to age-matched APPsw/0; Pdgfrβ+/+ littermates.

  3. X
    Cognitive Impairment at 41

    At nine months, APPsw/0;Pdgfrβ+/- mice perform poorly on several hippocampal-dependent behavioral tests including burrowing, nest construction, and novel object recognition, compared with age-matched APPsw/0;Pdgfrβ+/+ littermates.

Absent
No Data
  • Tangles at

    Although mature neurofibrillary tangles were not observed by 9 months (the oldest age assessed), the mice develop significant tau pathology, including tau hyperphosphorylation in cortical and hippocampal neurons. Pre-tangle pathology is observed, including neuronal caspase-cleaved tau, and conformational changes as indicated by the conformation-specific antibody MC1.

  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PDGFRB APP K670_M671delinsNL (Swedish) APP: Transgenic; PDGFRB: Knock-Out Alzheimer's Disease

Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus.

Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition.

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APPSwDI x NOS2 Knock-out

Observed
  1. X
    Plaques at 49

    Aβ deposits by 52 weeks. Particularly dense Aβ immunoreactivity in the subiculum and thalamus, including in the cerebral microvessels (Wilcock et al., 2008).

  2. X
    Tangles at 49

    Extensive tau pathology by 52 weeks, including intraneuronal aggregates of hyperphosphorylated tau. Increased phosphorylated tau in bigenic mice compared to APPSwDI mice (Wilcock et al., 2008).

  3. X
    Neuronal Loss at 52

    Significant neuron loss by 52 weeks in the hippocampus and subiculum, especially of neuropeptide Y neurons. Numerous Fluoro-Jade C+ neurons: 30% loss in the hippocampus, 35% loss in the subiculum (Wilcock et al., 2008).

  4. X
    Cognitive Impairment at 53

    Impairments in spatial memory by 52-56 weeks as measured by the radial arm maze and the Barnes maze. Bigenic mice more impaired than APPSwDI (Wilcock et al., 2008).

Absent
No Data
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, NOS2 APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) APP: Transgenic; NOS2: Knock-Out Alzheimer's Disease

Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone.

Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks.

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APP(Swedish) (R1.40)

Observed
  1. X
    Plaques at 59

    By 13.5 months homozygous mice develop both parenchymal and vascular amyloid deposits which first appear in the frontal cortex. No Aβ deposition at 5 months (Lehman et al., 2003).

  2. X
    Gliosis at 61

    Reactive astrocytes and microglia in 14-16 month old animals (Kulnane et al., 2001).

Absent
  • Tangles at

    No mature tangles, but some changes in phosphorylated tau.

  • Changes in LTP/LTD at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish) APP: Transgenic Alzheimer's Disease

By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months.

Unknown.

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APPSwe (line C3-3)

Observed
  1. X
    Plaques at 104

    Some plaque formation at advanced age (24-26 months) (Savonenko et al., 2003).

Absent
  • Cognitive Impairment at

    Normal reference and working memory up to 12-14 months on congenic background (Savonenko et al., 2003).

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish) APP: Transgenic Alzheimer's Disease

Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age.

Congenic animals showed normal reference and working memory up to 12-14 months.

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APPSwe/PSEN1(A246E)

Observed
  1. X
    Plaques at 39

    By 9 months of age, amyloid plaques develop in the hippocampus and subiculum, later extending to the cortex (Borchelt et al., 1997). The striatum and thalamus are relatively spared out to 18 months of age. Amyloid pathology is more severe in female mice, with a greater amyloid burden measured at 12 and 17 months of age (Wang et al., 2003).

  2. X
    Gliosis at 52

    By one year of age, reactive gliosis is observed in the cortex and hippocampus and is associated with dystrophic neurites (Borchelt et al., 1997).

  3. X
    Cognitive Impairment at 48

    Age-associated cognitive impairment, as measured by the Morris water maze, was observed in 11 to 12-month-old males. Both acquisition and retention were impaired. No impairment at 3-4 months of age. At both time points mice performed normally on a position discrimination task in the T-maze (Puoliväli et al., 2002).

Absent
  • Tangles at

    Not observed.

  • Neuronal Loss at

    There was no difference in neuronal numbers in the cingulate cortex compared with wild-type mice (Xiang et al., 2002).

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 A246E APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus.

Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task.

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APPSwe/PSEN1dE9 (C3-3 x S-9)

Observed
  1. X
    Plaques at 26

    Plaques are present in the hippocampus and cortex by 6 months of age.

  2. X
    Cognitive Impairment at 78

    Age-related cognitive deficits. Episodic memory appears to be more sensitive than reference memory. No differences at 6 months of age, but detectable at 18 months (Savonenko et al., 2005).

Absent
  • Tangles at

    Not observed.

No Data
  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers.

Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months.

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APPswe/PSEN1dE9 (C57BL6)

Observed
  1. X
    Plaques at 16

    Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months.

  2. X
    Gliosis at 17

    Plaque-associated astrogliosis and microgliosis are evident by 4 and 8 months, respectively.

  3. X
    Synaptic Loss at 18

    Synapse loss in the hippocampus occurs by 4 months.

  4. X
    Cognitive Impairment at 40

    Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age.

Absent
  • Tangles at

    Not observed.

  • Neuronal Loss at

    Neuron loss has not been observed in mice up to 12 months of age.

No Data
  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months. Gliosis and dystrophic neurites are associated with plaques. Amyloid angiopathy has been observed in the retina.

Hyperactivity is apparent by 6 months. Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age.

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APPswe/PSEN1dE9 (line 85)

Observed
  1. X
    Plaques at 26

    Occasional Aβ deposits can be found by 6 months, with abundant plaques in the hippocampus and cortex by 9 months (Jankowsky et al., 2004) and a progressive increase in plaques up to 12 months (Garcia-Alloza et al., 2006).

  2. X
    Neuronal Loss at 35

    Neuronal loss observed adjacent to plaques relative to more distal areas.

  3. X
    Gliosis at 26

    Minimal astrocytosis at 3 months; significant astrocytosis by 6 months, especially in areas around plaques. Extensive GFAP+ staining at 15 months and later throughout the cortex (Kamphuis et al., 2012).

  4. X
    Synaptic Loss at 17

    In the B6 congenic mice, age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and Homer immunoreactivity in the hippocampus by 4 months (Hong et al., 2016).

  5. X
    Changes in LTP/LTD at 13

    Transient long-term potentiation (t-LTP) is reduced by 3 months. The degree of impairment is not related to age from 3 to 12 months (Volianskis et al., 2008).

  6. X
    Cognitive Impairment at 52

    Impairment in the Morris water maze at 12 months, specifically during acquisition of the hidden platform sub-task and the probe trial, but not in the visible platform test (Lalonde et al., 2005). At 13 months the mice commit more errors in the Morris water maze, but not at 7 months (Volianskis et al., 2008).

Absent
  • Tangles at

    Not observed.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity.

Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing).

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APP(V642I)KI

Observed
  1. X
    Cognitive Impairment at 117
    Impairments at the water finding task at age 27-29 months, a test of long-term memory. No differences in the open field test of the elevated plus maze indicating no difference in general behavioral patterns, activity level, or emotional state.
Absent
  • Plaques at

    Absent.

  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP V717I (London) APP: Transgenic Alzheimer's Disease

Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy.

At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels.

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APP(V717I)

Observed
  1. X
    Plaques at 43

    Plaques start in the cortex and subiculum at ~10 months. Diffuse amyloid deposits and compact neuritic plaques at 13-18 months especially in the hippocampus and cortex, with occasional deposits in the thalamus and fimbria, external capsule, pontine nuclei, and white matter (Moechars et al., 1999). Prominent amyloid deposits in brain vessels after 15 months (Van Dorpe et al, 2000).

  2. X
    Gliosis at 43

    GFAP, microglial activation, and other markers of brain inflammation are elevated by 10 months.

  3. X
    Changes in LTP/LTD at 26

    Significant deficit in LTP in CA1 region of the hippocampus at 6 months.

  4. X
    Cognitive Impairment at 26

    From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze and other tests. Also deficits in associative learning.

Absent
  • Tangles at

    Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP V717I (London) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.

From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression.

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APP(V717I) x PS1(A246E)

Observed
  1. X
    Plaques at 17

    Plaques start in cortex, hippocampus and subiculum at 4-6 months.

  2. X
    Gliosis at 20

    Elevated GFAP, microglial activation, and other markers of brain inflammation increase as of 4.5 months.

  3. X
    Changes in LTP/LTD at 26

    Significant deficit in LTP in CA1 region of the hippocampus at 6 months.

  4. X
    Cognitive Impairment at 22

    From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris water maze and other tests. Also deficits in associative learning.

Absent
  • Tangles at

    Dystrophic neurites containing hyperphosphorylated murine tau, but no tangle pathology.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP V717I (London), PSEN1 A246E APP: Multi-transgene; PSEN1: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology.

From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression.

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Arc48 (APPSw/Ind/Arc)

Observed
  1. X
    Plaques at 9

    Parenchymal neuritic plaques by 2 months with prominent plaque deposition in the hippocampus by 3-4 months. Abundant mature thioflavin-S positive plaques with dystrophic neurites by 10-12 months (Cheng et al., 2007).

  2. X
    Gliosis at 13

    Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).

  3. X
    Cognitive Impairment at 13

    At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but were impaired in the ability to use extramaze cues to navigate to the hidden platform (Cheng et al., 2007).

Absent
  • Tangles at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20.

At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform.

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ArcAβ

Observed
  1. X
    Plaques at 39

    Between 9 and 15 months of age β-amyloid plaques became prominent. Plaques had a characteristic dense core morphology which differed from the cotton wool-like structure of plaques seen with the Swedish mutation alone (Knobloch et al., 2007).

  2. X
    Changes in LTP/LTD at 15

    LTP is severely impaired in slices from 3.5 and 7.5 month old mice. LTP and basal synaptic transmission were normal in slices from one month old mice (Knobloch et al., 2007).

  3. X
    Cognitive Impairment at 26
    Cognitive impairment measured from the age of 6 months in the Morris water maze and Y-maze, as well as in active avoidance behavior (Knobloch et al., 2007).
Absent
  • Tangles at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma.

Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze.

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ARTE10

Observed
  1. X
    Plaques at 13

    Robust and reliable plaque pathology as early as 3 months in homozygotes, 5 months in hemizygotes. Plaques start in the anterior neocortex and subiculum, spreading to other brain regions (e.g. hippocampus, thalamus, amygdala). Congophilic dense-core plaques are abundant, with lower levels of diffuse plaques and some cerebral amyloid angiopathy.

  2. X
    Gliosis at 22

    Glial activation, including reactive astrocytes and activated microglia, is present in areas around plaques by 5 months of age in homozygous animals, later in hemizygotes.

  3. X
    Synaptic Loss at 13

    Decreased expression of synaptophysin mRNA in the brain by 3-4 months of age in both hemizygous and homozygous animals.

  4. X
    Cognitive Impairment at 52

    Select, paradigm-dependent, deficits in learning and memory, especially episodic memory, by 12 months in homozygous and hemizygous mice.

Absent
  • Tangles at

    No tangles or neuropil threads, but some hyperphosphorylated tau by eight months in dystrophic neurites.

  • Neuronal Loss at

    Outright neuronal loss has not been documented, but substantial degeneration of dendritic arbors occurs by 10-14 months of age in hippocampal neurons.

No Data
  • Changes in LTP/LTD at

    Unknown; however, hippocampal neurons exhibit substantial changes in electrophysiological properties by 10-14 months of age, including hyperexcitability in the form of increased firing of action potentials and a more efficient transition from solitary firing to bursting.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 M146V APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches.

Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months.

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Atg16LΔWD

Observed
  1. X
    Neuronal Loss at 104

    Apparent neuron loss in hippocampi of 2-year-old mice (fewer neurons, increased levels of cleaved caspase-3, and increased numbers of TUNEL-positive neurons).

  2. X
    Gliosis at 104

    Microgliosis in the hippocampi of 2-year-old mice.

  3. X
    Changes in LTP/LTD at 104

    Impaired long-term potentiation at CA3-CA1 synapses.

  4. X
    Cognitive Impairment at 104

    Deficits in the sucrose preference test, spontaneous alternation in the Y-maze, and novel object recognition test.

Absent
  • Plaques at

    Intracellular and extracellular Aβ deposits, but no dense-core plaques, in 2-year-old mice.

No Data
  • Tangles at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Atg16l1 Atg16l1: Knock-Out Alzheimer's Disease

Intracellular and extracellular Aβ deposits, but no dense-core plaques. Microgliosis and neuron loss in 2-year-old mice.

Deficits in the sucrose-preference test, spontaneous alternation in the Y-maze, and novel object recognition test.

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BACE1 cKO (Hu, Yan) X 5xFAD

Observed
  1. X
    Plaques at 11

    Accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.

  2. X
    Gliosis at 11

    Reactive astrocytes and microglia accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.

  3. X
    Changes in LTP/LTD at 40

    Deficit in LTP at Schaffer collateral–CA1 synapses, but less severe than in control 5xFAD mice.

Absent
  • Cognitive Impairment at

    Cued and contextual fear conditioning normal, tested at eight to 10 months of age.

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter.

Normal contextual and cued fear conditioning, tested at 8 to 10 months of age.

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Bace1 conditional knock-out (adult, whole body) (Vassar)

Observed
Absent
  • Changes in LTP/LTD at

    LTP at Schaffer collateral–CA1 synapses was similar in slices obtained from 12-month BACE1-deficient and control mice.

  • Cognitive Impairment at

    Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning when tested at 9 months of age.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

Defects in axonal organization.

Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations.

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BACE1 conditional knock-out (Hu, Yan)

Observed
  1. X
    Changes in LTP/LTD at 40

    Long-term potentiation at Schaffer collateral–CA1 synapses impaired in slices obtained from 10- to 12-month-old mice.

Absent
  • Plaques at

    Not observed.

  • Tangles at

    Not observed.

  • Neuronal Loss at

    Not observed.

  • Gliosis at

    No astrogliosis at 1-2 months.

  • Cognitive Impairment at

    Contextual and cued fear conditioning normal at 8-10 months.

No Data
  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

No gross morphological changes observed.

BACE1-deficient mice and Bace1fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age.

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Bace1 conditional knock-out (neonatal, forebrain) (Vassar)

Observed
  1. X
    Cognitive Impairment at 24

    Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning.

Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

Hypomyelination and defects in axon organization.

Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments.

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Bace1 conditional knockout (Tesco)

Observed
  1. X
    Changes in LTP/LTD at 60

    Deficit in long-term potentiation at Schaffer collateral–CA1 synapses in slices from 14-month-old animals that had received tamoxifen between 8 and 12 weeks of age.

Absent
  • Cognitive Impairment at

    Animals that had received tamoxifen between 8 and 12 weeks of age were tested at 4–5 or 12–14 months. Tamoxifen-treated mice performed similarly to vehicle-treated controls in the Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition tests.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Bace1 Bace1: Conditional Knock-out Alzheimer's Disease

None observed: hippocampal mossy fiber organization and sciatic-nerve myelination were normal.

Performed similarly to controls in a battery of tests (Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition task).

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BRI-Aβ42 (BRI2-Aβ42)

Observed
  1. X
    Plaques at 13

    Detergent-insoluble amyloid-β and cored plaques as early as three months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices by 12 months. Extensive congophillic amyloid angiopathy.

  2. X
    Gliosis at 13

    Plaque-associated reactive gliosis as measured by GFAP immunostaining.

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

  • Cognitive Impairment at

    On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss.

On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.

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CAST.APP/PS1

Observed
  1. X
    Plaques at 32

    Thioflavin S-positive amyloid plaques are present in the cortex and hippocampus by 8 months of age, with more severe plaque pathology in females than in males.

  2. X
    Neuronal Loss at 34

    Compared with their non-transgenic littermates, CAST.APP/PS1 mice have fewer neurons in area CA1 of the hippocampus. Cortical neuron numbers do not differ between the genotypes.

  3. X
    Gliosis at 33

    Plaque-associated microgliosis observed by 8 months.

  4. X
    Cognitive Impairment at 31

    Deficits in short-term memory by 8 months in males (data from females unavailable).

Absent
  • Tangles at

    Not observed.

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in hippocampal area CA1.

Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in males (data from females is not available, as wild-type females are unable to perform this test).

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Ceacam1 KO/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, Ceacam1, Trem2 TREM2 R47H APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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Clasp2*L163P/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Clasp2, APOE, Trem2 TREM2 R47H Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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E2FAD

Observed
  1. X
    Plaques at 17

    Plaques develop in the subiculum and deep cortical layers by 4 months.

  2. X
    Gliosis at 26

    Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

  3. X
    Synaptic Loss at 17

    Protein levels of  NMDA receptor subunits decreased from 2 to 6 months.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    E2FAD mice had performance in learning and memory tasks comparable to E3FAD animals and better than E4FAD mice.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.

In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice.

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E3FAD

Observed
  1. X
    Plaques at 17

    Plaques develop in the subiculum and deep cortical layers by 4 months.

  2. X
    Gliosis at 26

    Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

  3. X
    Synaptic Loss at 17

    Protein levels of  NMDA receptor subunits decreased from 2 to 6 months.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    E3FAD mice had performance in learning and memory tasks comparable to E4FAD and E2FAD animals.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.

In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice.

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E4FAD

Observed
  1. X
    Plaques at 17

    Plaques develop in the subiculum and deep cortical layers by 4 months.

  2. X
    Gliosis at 26

    Microgliosis and astrocytosis in the subiculum and cortex at 6 months.

  3. X
    Synaptic Loss at 17

    Decreased protein levels of PSD95 and NMDA receptor subunits by 4 months.

  4. X
    Cognitive Impairment at 8

    Modest learning deficits in the Morris water maze by 2 months. Progressive decrease in performance on learning and memory tasks. 

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. 

Age-dependent learning and memory deficits in the Y maze and Morris water maze.

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hAbeta/APOE4/Trem2*R47H (LOAD2)

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, APP, Trem2 TREM2 R47H APOE: Knock-In; APP: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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hAbeta-loxP-KI

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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hAβ-KI

Observed
  1. X
    Synaptic Loss at 78

    Fewer synaptophysin-immunoreactive puncta, but similar numbers of PSD95-immunoreactive puncta, in knock-in mice compared with wild-type mice.

  2. X
    Changes in LTP/LTD at 78

    Impaired theta-burst-induced LTP at Schaffer collateral-CA1 synapses, by 18 months of age.

  3. X
    Cognitive Impairment at 40

    Differed from wild-type mice in the contextual fear conditioning test by 10 months of age and in the novel object recognition task by 14 months.

Absent
  • Plaques at

    No plaques observed through 22 months of age, using immunohistochemical, thioflavin-S or Congo red stains.

  • Neuronal Loss at

    Neuron numbers in hippocampal CA1 were similar in 22-month hAβ-KI and wild-type mice, although hippocampal volume was decreased in the knock-in mice.

  • Gliosis at

    Neither microgliosis nor astrogliosis was observed through 22 months of age.

No Data
  • Tangles at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App App: Knock-In Alzheimer's Disease

No amyloid plaques observed through 22 months of age. Accelerated formation of OC-immunoreactive and Periodic Acid Schiff-positive granules.

Differed from wild-type mice in the contextual fear conditioning test by 10 months of age and in the novel object recognition task by 14 months.

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hCR1 KI on APOE4/Trem2

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Cr2, CR1, CR2, APOE, Trem2 TREM2 R47H Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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htau

Observed
  1. X
    Tangles at 39

    Aggregated tau and paired helical filaments detectable at nine months by immunoelectron microscopy, although paired helical filaments of aggregated insoluble tau can be isolated from brain tissue as early as two months. Tau first redistributes from axons to cell bodies. Hyperphosphorylated tau begins to accumulate by six months, and increases further by 13 and 15 months (Andorfer et al., 2003).

  2. X
    Neuronal Loss at 43

    Decrease in cortical thickness and reduced cell number between 10 and 14 months of age. Increased ventricle size increased from age eight months to 18 months. Decrease in the thickness of the corpus callosum (Andorfer et al., 2005).

  3. X
    Changes in LTP/LTD at 52

    In hippocampal slices, LTP induced by high frequency stimulation (HFS) was normal at four months but abolished by 12 months. LTP induced by theta burst stimulation (TBS) was normal at both ages. Paired-pulse ratio (PPR) was unaffected at four months, but increased at 12 months compared with controls, suggesting a decrease in probability of transmitter release (Polydoro et al., 2009).

  4. X
    Cognitive Impairment at 26

    Abnormal spatial learning in six-month-old mice compared with control mice (Phillips et al., 2011). Normal object recognition and spatial learning and memory by MWM at four months, but deficits by 12 months (Polydoro et al., 2009). Impaired burrowing relative to control mice occurs by four months (Geiszler et al., 2016).

Absent
No Data
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT: Knock-Out; MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

Age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately thioflavin-S positive neurofibrillary tangles. Pathology most severe in neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some neuronal loss.

Normal object-recognition memory and spatial learning/memory (as assessed by the Morris Water Maze) at four months, but impaired at 12 months (Polydoro et al., 2009). 

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hTau-A152T

Observed
  1. X
    Neuronal Loss at 87

    Neuron loss in the hippocampus was observed by 20 months.

  2. X
    Gliosis at 17

    Astrocytosis, but no differences in microglia.

  3. X
    Cognitive Impairment at 74

    In the Morris water maze, performance was impaired after 17 months of age. Nest building was impaired at 10-14 months. Social interaction, anxiety, exploratory behavior, and motor functions were unaltered.

Absent
  • Tangles at

    Abnormal accumulations of soluble tau were observed, but not tangles or tangle-like structures.

  • Changes in LTP/LTD at

    Unchanged at 20 months.

No Data
  • Plaques at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT A152T MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus.

Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal.

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hTau-AT (hTau40-AT)

Observed
  1. X
    Tangles at 13

    Tangles in hippocampus, cortex, and spinal cord starting at 3 months with age-dependent increases. Hyperphosphorylation, conformation changes, and mislocalization.

  2. X
    Neuronal Loss at 52

    Neuron loss in the hippocampus and cortex at 12 months.

  3. X
    Gliosis at 43

    Astrocytosis and microgliosis at 10 months.

  4. X
    Synaptic Loss at 87

    Synaptophysin, but not PSD95, decreased in hippocampus and cortex at 12 months. By Golgi staining, spines unchanged in CA1 at 10 months, increased in CA3 at 12 months, and decreased in CA1 and CA3 at 16 months.

  5. X
    Cognitive Impairment at 70

    No change at 10 months but at 16 months deficits in learning and memory (Morris water maze).

Absent
  • Changes in LTP/LTD at

    Unchanged at 12 months.

No Data
  • Plaques at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT A152T MAPT: Knock-In Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses.

Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal.

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hTau.P301S

Observed
  1. X
    Tangles at 17

    Neurofibrillary tangles detected as early as 4 months of age.

  2. X
    Neuronal Loss at 13

    Neuronal loss starting at 3 months. Loss is especially prominent in the spinal cord with notable loss of superficial cortical neurons as well (Hampton et al., 2010).

  3. X
    Gliosis at 22

    Astrocytosis, as measured by GFAP reactivity, in 6 month-old animals. Microglial activation in the brain stem and spinal cord of 5 month-old animals by OX42 staining (Bellucci et al., 2004).

  4. X
    Cognitive Impairment at 11

    Memory deficit starting at 2.5 months as assessed by the Morris water maze (Xu et al., 2014), but no deficit at 2 months (Scattoni et al., 2010).

Absent
  • Plaques at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301S MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis.

Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months.

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hTREM2-KI

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
TREM2 TREM2: Knock-In Alzheimer's Disease

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hTREM2-R47H_KI

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
TREM2 TREM2 R47H TREM2: Knock-In Alzheimer's Disease

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Il1rap KO/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, Il1rap, Trem2 TREM2 R47H APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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J20 (PDGF-APPSw,Ind)

Observed
  1. X
    Plaques at 22

    At 5-7 months of age diffuse amyloid-β plaques deposit in the dentate gyrus and neocortex. Amyloid deposition is progressive with widespread plaques by 8-10 months. Aβ puncta are deposited in the hippocampus as early as 1 month (Hong et al., 2016).

  2. X
    Neuronal Loss at 12

    Cell loss varies by brain region. No significant neuronal loss was observed in the CA3 region of the hippocampus at 6, 12, 24 and 36 weeks of age nor in the CA1 region at 6 weeks; however, at 12, 24, and 36 weeks significant neuronal loss was observed in the CA1 region compared to age-matched wild-type animals (Wright et al., 2013).

  3. X
    Gliosis at 24

    At 24 and 36 weeks a significant increase in the number of reactive GFAP+ astrocytes and CD68+ microglia was observed in the hippocampi of J20 mice compared to age-matched wild-type controls. No significant difference was observed at 6 and 12 weeks (Wright et al., 2013).

  4. X
    Synaptic Loss at 15

    Age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and homer immunoreactivity in the hippocampus by 3 months; synapse loss was confirmed by electron microscopy. No significant difference was seen at 1 month (Hong et al., 2016).

  5. X
    Changes in LTP/LTD at 13

    Basal synaptic transmission is impaired between 3-6 months; extracellularly recorded field EPSPs at the Schaffer collateral to CA1 synapse in acute hippocampal slices were on average smaller in amplitude than those seen in wild-type mice. Significant deficits in LTP at the Schaffer collateral–CA1 synapse compared with control mice at 3-6 months (Saganich et al., 2006).

  6. X
    Cognitive Impairment at 16

    Deficits in spatial memory and learning appear as the mice age. By 4 months, J20 mice demonstrate spatial reference memory deficits as measured by the radial arm maze (Wright et al., 2013) and Morris water maze (Cheng et al., 2007).

Absent
  • Tangles at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity.

Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated.

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JNPL3(P301L)

Observed
  1. X
    Tangles at 20

    Neurofibrillary tangles develop in an age and gene-dose dependent manner; as early as 4.5 months in homozygotes and 6.5 months in heterozygotes. Tangles and Pick-body-like neuronal inclusions in the amygdala, septal nuclei, preoptic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord (Lewis et al., 2000).

  2. X
    Neuronal Loss at 43

    Neuronal loss, especially in the spinal cord, most prominent in the anterior horn (Lewis et al., 2000).

  3. X
    Gliosis at 43

    Astrogliosis (as measured by GFAP reactivity) in brainstem, diencephalon, and basal telencephalon by 10 months (Lewis et al., 2000).

Absent
  • Plaques at

    Absent.

No Data
  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Transgenic Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease

Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord.

By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization.

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Kif21b*T82T/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Kif21b, APOE, Trem2 TREM2 R47H Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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MAPT(H1.0)-GR

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, MAPT-AS1, Mapt MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Unknown.

Unknown.

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MAPT(H2.1)-GR

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, MAPT-AS1, Mapt MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Unknown.

Unknown.

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MAPT knock-in

Observed
Absent
  • Plaques at

    No amyloid plaques at 24 months of age.

  • Tangles at

    No neurofibrillary tangles at 24 months of age.

  • Neuronal Loss at

    Neurodegeneration not apparent up to 2 years of age.

  • Gliosis at

    No astrogliosis or microgliosis observed at 24 months.

  • Cognitive Impairment at

    At 12 months of age, MAPT knock-in mice perform similarly to wild-type mice in the Y-maze test of working memory (only males tested).

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT: Knock-In Alzheimer's Disease, Other Tauopathy

No evidence of increased neuroinflammation, neuronal death, or brain atrophy in MAPT knock-in mice, compared with wild-type mice.

MAPT knock-in mice perform similarly to wild-type mice in the Y-maze test of working memory.

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McGill-R-Thy1-APP

Observed
  1. X
    Plaques at 24

    Amyloid plaques present in homozygotes, appearing in hippocampus at 6 months and cortex at 13 months. Plaques are generally absent in hemizygotes.

  2. X
    Neuronal Loss at 72

    A 22 percent reduction in the number of neurons was seen in the subiculum of homozygous transgenic rats at 18 months.

  3. X
    Gliosis at 24

    Microgliosis and astrogliosis observed in homozyogotes.

  4. X
    Synaptic Loss at 80

    Reduction in cholinergic synaptic boutons seen at 20 months in homozygous transgenic rats.

  5. X
    Changes in LTP/LTD at 14

    Impairments in long-term potentiation in CA1 by 3.5 months of age.

  6. X
    Cognitive Impairment at 12

    Deficits in Morris water maze and fear conditioning test are apparent by 3 months of age in both hemizygous and homozygous transgenic rats.

Absent
No Data
  • Tangles at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

Hemizygotes: intraneuronal Aβ in hippocampus and cortex by one week, but no plaques even at advanced ages. Homozygotes: intraneuronal Aβ in hippocampus and cortex by one week; amyloid plaques in hippocampus beginning at 6 months, in cortex beginning at 13 months.

Cognitive deficits are apparent by three months of age in both hemizygous and homozygous transgenic rats.

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Mthfr*C677T/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Mthfr, APOE, Trem2 TREM2 R47H Mthfr: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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mThy-1 3R Tau (line 13)

Observed
  1. X
    Tangles at 34

    Pick-body like inclusions of aggregated tau appeared in the hippocampus and cortex by 8-10 months. Inclusions were positive for Bielchowsky silver stain but negative for Gallyas-silver stain and Thioflavin-S.

  2. X
    Neuronal Loss at 34

    Neuronal loss occurred by 8-10 months as evidenced by decreased NeuN staining in the dentate gyrus and CA3 regions of the hippocampus. Neocortical volume also decreased.

  3. X
    Gliosis at 35

    Astrogliosis was seen by 8-10 months in the neocortex and hippocampus. Some GFAP+ astrocytes also contained 3R tau.

  4. X
    Cognitive Impairment at 26

    By 6-8 months memory impairment was evident as a failure to habituate to a novel environment. This deficit was not present at 3-4 months. At 8-10 months, transgenics also took longer than wild-type mice to find the hidden platform in the Morris water maze.

Absent
  • Plaques at

    Absent.

No Data
  • Synaptic Loss at

    Synapto-dendritic damage manifested as reduced dendritic density, reduced MAP2 immunoreactivity, and accumulation of 3R tau in dendrites.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT L266V, MAPT G272V MAPT: Transgenic Frontotemporal Dementia, Pick's disease, Alzheimer's Disease

Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology.

Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test.

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mThy1-hAPP751 (TASD41)

Observed
  1. X
    Plaques at 13

    Plaques start at 3-6 months in the frontal cortex and become widespread with age, affecting the piriform and olfactory cortices, hippocampus, and thalamus (Rockenstein et al., 2001; Havas et al., 2011).

  2. X
    Gliosis at 27

    Inflammation related to activated microglia (increased CD11) and reactive astrocytes (increased GFAP) is significant by 6 months and increases with age.

  3. X
    Synaptic Loss at 52

    Dystrophic neurites and synaptic loss starting at 12 months.

  4. X
    Cognitive Impairment at 26

    Cognitive impairment observed by 6 months by Morris Water Maze (Rockenstein et al., 2005).

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

No Data
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP V717I (London) APP: Transgenic Alzheimer's Disease

Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region.

Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration.

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NSE-APP751

Observed
  1. X
    Plaques at 8

    Aβ deposits were observed as early as two months of age. These deposits were diffuse and extracellular and had a “cotton-like” appearance. Classic mature plaques were not observed.

  2. X
    Gliosis at 95

    Gliosis was noted in a single 22-month-old animal with extensive Aβ deposits (Higgins et al., 1994).

  3. X
    Cognitive Impairment at 52

    Deficits in spatial memory and learning appear as the mice age. At 12 months the mice demonstrate learning and memory deficits as measured by a water-maze task and in spontaneous alternation in a Y maze (Moran et al., 1995). At six months cognition is largely normal.

Absent
  • Tangles at

    Classic tangles were not observed, but aberrant tau immunoreactivity was observed as early as two months.

  • Neuronal Loss at

    Cell death was not formally assessed, however, overt neuronal death was not seen.

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP: Transgenic Alzheimer's Disease

Age-dependent increase in Aβ deposits and tau immunoreactivity.

Learning and memory deficits are age-dependent as assessed on spontaneous alternation in a Y maze and in the water-maze task.

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PA-Rab5

Observed
  1. X
    Neuronal Loss at 28

    Loss of basal forebrain cholinergic neurons, beginning at 7 months.

  2. X
    Synaptic Loss at 34

    Loss of spines in CA3 and dentate gyrus regions of the hippocampus, observed in 8.5-month-old mice.

  3. X
    Changes in LTP/LTD at 24

    Pronounced defect in LTD and slight impairment in LTD at Schaffer collateral-CA1 synapses in hippocampal slices from 6-month-old mice.

  4. X
    Cognitive Impairment at 24

    When tested at 6 months of age, the performance of PA-Rab5 mice differed from wild-type controls in a novel object recognition test.

Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Gliosis at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
RAB5A RAB5A: Transgenic Alzheimer's Disease

Enlarged Rab5-positive endosomes, tau hyperphosphorylation, synapse loss in hippocampus, and loss of basal forebrain cholinergic neurons.

When tested at 6 months of age, the performance of PA-Rab5 mice differed from wild-type controls in a novel object recognition test.

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PDAPP(line109)

Observed
  1. X
    Plaques at 26

    In heterozygous mice no plaque pathology at 4-6 months. At 6-9 months mice begin to exhibit deposits of human Aβ in the hippocampus, corpus callosum, and cerebral cortex. Plaques become more extensive with age and vary in size and structure including diffuse irregular plaques and compact cored plaques (Games et al., 1995).

  2. X
    Gliosis at 26

    GFAP-positive astrocytes and activated microglia associated with plaques (Games et al., 1995).

  3. X
    Synaptic Loss at 35

    Decreased synaptic density in the dentate gyrus as measured by synaptophysin immunoreactivity. Also decreased dendritic density as measured by MAP2 immunoreactivity (Games et al., 1995).

  4. X
    Changes in LTP/LTD at 17

    Alterations in LTP induced by theta burst stimulation at 4-5 months which is prior to plaque formation; although the potentiation immediately after TBS was comparable to control mice, the potentiation decayed more rapidly in PDAPP mice. Also paired pulse facilitation was enhanced. Responses to high frequency stimulation bursts were distorted (Larson et al., 1999).

  5. X
    Cognitive Impairment at 13

    Deficits in a variety of memory paradigms from a young age. Robust deficits in the radial arm maze at 3 months (deficits appear before amyloid plaque deposits). Object recognition, 6, 9-10 months. Operant learning, 3, 6 months (Dodart et al., 1999).

Absent
  • Tangles at

    No paired helical filaments or aggregates, but phosphorylated tau immunoreactivity is observed in dystrophic neurites after 14 months (Masliah et al., 2001).

  • Neuronal Loss at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus.

Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months.

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PDGF-APP(WT) (line I5)

Observed
  1. X
    Synaptic Loss at 9

    By 2-4 months of age, there is a decrease in synaptophysin-immunoreactive presynaptic terminals compared to nonTg controls. Synaptophysin immunoreactivity decreases further with age.

Absent
  • Tangles at

    Not observed.

  • Neuronal Loss at

    Not observed.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP: Transgenic Alzheimer's Disease

Expression of human APP in the brain especially in the neocortex and hippocampus. No plaques up to 24 months.

Unknown.

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PLB1-triple (hAPP/hTau/hPS1)

Observed
  1. X
    Gliosis at 52

    Increased inflammation (GFAP labelling) detected at 12 months in cortex and hippocampus (Platt, unpublished observation).

  2. X
    Changes in LTP/LTD at 26

    Impairments in long-term and short-term hippocampal plasticity. LTP following theta-burst stimulation decayed faster and paired-pulse facilitation was reduced relative to wild-type mice at both six and 12 months of age. Synaptic transmission impacted at 12 months.

  3. X
    Cognitive Impairment at 22

    Social recognition memory was impaired by five months and further impaired by 12 months. Similarly, object recognition memory was impaired by eight months. Spatial learning impairments were seen later; at 12 months deficits in spatial acquisition learning were seen in the open field water maze that were not apparent at 5 months.

Absent
  • Plaques at

    Sparse plaques out to 21 months of age. Only marginally increased compared with wild-types and overall very low compared to over-expression models. However, Aβ accumulated intracellularly and also formed oligomers.

  • Tangles at

    No overt tangle pathology; however, hyyperphosphorylated tau accumulated in the hippocampus and cortex from six months of age.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, MAPT, PSEN1 APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene Alzheimer's Disease

Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT.

Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity.

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PLB4 (hBACE1)

Observed
  1. X
    Gliosis at 52

    Increased GFAP-positive astrocytes at 12 months of age in the dentate gyrus, CA1 region of the hippocampus, and the piriform cortex. Gliosis is suspected to begin earlier than 12 months.

  2. X
    Cognitive Impairment at 13

    Impaired spatial representation in a habituation task by 3 months of age. By 6 months, impaired learning and memory by a variety of tasks including the Y-maze, Morris water maze, and a test of the social transmission of food preference. These effects appear to be distinct from reduced motor activity and reduced anxiety.

Absent
  • Plaques at

    Plaques virtually absent, minimal small sparse plaques. However, prominent extracellular Aβ staining surrounding neuronal cell bodies, including Aβ multimers (e.g. Aβ*56 and Aβ hexamers).

  • Tangles at

    Preliminary analysis did not find abnormal phosphorylation or conformational changes in tau.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
BACE1 BACE1: Transgenic Alzheimer's Disease

Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology.

Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety.

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Plcγ2-P522R knock-in

Observed
  1. X
    Gliosis at 24

    Astrogliosis revealed by GFAP immunohistochemistry in 6-month-old males. Microglial activation revealed by TSPO PET imaging in year-old females.

Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Plcg2 Plcg2: Knock-In Alzheimer's Disease, Dementia with Lewy Bodies, Frontotemporal Dementia

Hypertrophic astrocytes in the hippocampi, revealed by GFAP immunohistochemistry. Microglial activation revealed by TSPO PET imaging.

Unknown.

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Plcg2 KO

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Plcg2 Plcg2: Knock-Out Alzheimer's Disease

Unknown.

Unknown.

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Plcg2*M28L/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APOE, Plcg2, Trem2 TREM2 R47H APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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Plcg2*M28L x 5xFAD

Observed
  1. X
    Plaques at 30

    Diffuse and compact amyloid plaques observed in mice studied at 7.5 months of age. Higher plaque burdens than 5xFAD.

  2. X
    Gliosis at 31

    Microgliosis observed in mice studied at 7.5 months of age.

  3. X
    Synaptic Loss at 32

    Decreased basal synaptic transmission, lower frequencies and amplitudes of spontaneous excitatory postsynaptic currents and spontaneous inhibitory postsynaptic currents recorded in hippocampal CA1 region, compared with wild-type mice.

  4. X
    Changes in LTP/LTD at 33

    Impaired LTP at Schaffer collateral-CA1 synapses, compared with wild-type.

  5. X
    Cognitive Impairment at 24

    Deficits in working memory (decreased spontaneous alternation in the Y-maze), compared with wild-type.

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Plcg2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Plaque burdens in the cortex and subiculum were elevated in 5xFADM28L mice but microglia showed less interaction with plaques, compared with 5xFAD.

Six-month-old 5xFADM28L and 5xFAD mice showed similar deficits in working memory, assessed in the Y-maze.

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Plcg2*P522R

Observed
  1. X
    Gliosis at 24

    Plcg2*P522R knock-in mice had a slightly higher density of Iba1-positive microglia than wild-type mice. Microglia in the knock-in animals were simpler in shape—with less ramified processes—and contained a greater density of puncta immunoreactive for the lysosomal marker CD68, compared with wild-type microglia.

Absent
  • Synaptic Loss at

    Synapse number in hippocampal CA1—assessed as the density of puncta immunoreactive for the presynaptic marker bassoon or the postsynaptic marker PSD95—did not differ between Plcg2*P522R and wild-type mice. However, a slight decrease in the number of thin spines was observed in mutation carriers, while numbers of stubby and mushroom spines did not differ between the genotypes.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Plcg2 Plcg2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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Plcg2*P522R x 5xFAD

Observed
  1. X
    Plaques at 30

    Diffuse and compact amyloid plaques observed in mice studied at 7.5 months of age. Lower plaque burdens than 5xFAD.

  2. X
    Gliosis at 31

    Microgliosis observed in mice studied at 7.5 months of age.

Absent
  • Synaptic Loss at

    No deficits in synaptic transmission—including basal synaptic transmission, frequencies and amplitudes of spontaneous excitatory postsynaptic currents and spontaneous inhibitory postsynaptic currents, and AMPA/NMDA current ratios—recorded in hippocampal CA1 region of 7.5-month-old mice.

  • Changes in LTP/LTD at

    Normal LTP at Schaffer collateral-CA1 synapses at 7.5 months of age.

  • Cognitive Impairment at

    Normal working memory (spontaneous alternation in the Y-maze) at 6 months of age.

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Plcg2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Plaque burdens in the cortex and subiculum were lower in 5xFADP522R mice and microglia showed increased interaction with plaques, compared with 5xFAD.

The PLCγ2 P522R variant protected against deficits in the Y-maze test of working memory in 5xFAD mice.

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Plcg2*P522R x APP NL-G-F

Observed
  1. X
    Plaques at 24

    ThioflavinS-positive amyloid plaques observed in mice studied at 6 months of age. Higher plaque burdens than APPNL-G-F.

  2. X
    Gliosis at 24

    Microgliosis observed in mice studied at 6 months of age. Attenuated microglia-plaque interactions in the hippocampus, compared with APPNL-G-F.

Absent
  • Synaptic Loss at

    The P522R variant attenuated the synapse loss observed in APPNL-G-F mice with wild-type PLCγ2.

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Plcg2, App APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) Plcg2: Knock-In; App: Knock-In Alzheimer's Disease

Sex- and region-dependent increases in plaque burden, and decreases in microglia-plaque interactions, in Plcg2*P552R x APPNL-G-F mice, compared with APPNL-G-F.

Unknown.

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PS19 with humanized TREM2 (common variant)

Observed
  1. X
    Tangles at 37

    Tangles revealed using antibody PG5 at 9 months.

  2. X
    Neuronal Loss at 38

    At 9 months, atrophy of hippocampus and entorhinal/piriform cortex and pronounced ventricular expansion. Thinning of the granule cell layer of the dentate gyrus and pyramidal cell layer of the piriform cortex, compared with PS19 mice carrying TREM2-R47H.

  3. X
    Gliosis at 39

    Elevated expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the R47H variant of TREM2.

  4. X
    Synaptic Loss at 40

    Fewer synapses and more dystrophic synapses, compared with PS19 mice carrying the R47H variant of TREM2.

Absent
No Data
  • Plaques at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, TREM2, Trem2 MAPT P301S MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia

Brain atrophy by 9 months of age. Increased microgliosis, astrogliosis and synapse loss, compared with PS19 mice carrying TREM2 with the R47H mutation.

Not known.

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PS19 with humanized TREM2 (R47H)

Observed
  1. X
    Tangles at 36

    Tangles revealed using antibody PG5 at 9 months.

Absent
No Data
  • Plaques at

    No data.

  • Neuronal Loss at

    No data relative to wild-type mice, but at 9 months of age, the volumes of the hippocampus and entorhinal/piriform cortex are larger, and the granule cell layer of the dentate gyrus and pyramidal cell layer of the piriform cortex are thicker, in PS19-TREM2R47H mice, compared with PS19 mice carrying the common variant of human TREM2.

  • Gliosis at

    At 9 months of age, decreased expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the common variant of TREM2, but no data relative to wild-type mice.

  • Synaptic Loss at

    At 9 months of age, more synapses and fewer dystrophic synapses, compared with PS19 mice carrying the common variant of TREM2, but no data relative to wild-type mice.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, TREM2, Trem2 MAPT P301S, TREM2 R47H MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia

Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2.

Not known.

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PS1 conditional Knock-out

Observed
  1. X
    Cognitive Impairment at 22

    Mild impairment of spatial learning and memory in the Morris water maze observed in 5 month-old mice (Yu et al., 2001).

Absent
  • Plaques at

    Absent.

  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

  • Changes in LTP/LTD at

    Mice at 3-6 months of age exhibit normal paired-pulse facilitation, LTP, and LTD in the Schaffer collateral pathway of the hippocampus (Yu et al., 2001).

No Data
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
PSEN1 PSEN1: Conditional Knock-out Alzheimer's Disease

Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments.

Subtle but significant deficits in long-term spatial memory in the Morris water maze.

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PS2APP

Observed
  1. X
    Plaques at 26

    Age-associated development of plaques: none at 3 months, overt Aβ deposition at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months (Ozmen et al., 2009; Weidensteiner et al. 2009).

  2. X
    Gliosis at 26

    Gliosis at 6 months (personal communication, Laurence Ozmen).

  3. X
    Changes in LTP/LTD at 43

    A strong increase in LTP and post-tetanic potentiation induced by tetanic stimulation in hippocampal slices of 10 month-old animals compared to wild-type mice (Poirier et al., 2010).

  4. X
    Cognitive Impairment at 35

    Cognitive impairment is detected by the Morris water maze (probe trial 2) at 8 and 12 months of age, not at 3 months (personal communication Laurence Ozmen).

Absent
  • Tangles at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN2 APP K670_M671delinsNL (Swedish), PSEN2 N141I APP: Transgenic; PSEN2: Transgenic Alzheimer's Disease

Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months.

Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months.

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PS2APP (PS2(N141I) x APPswe)

Observed
  1. X
    Plaques at 39

    Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution over time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei (Richards et al., 2003).

  2. X
    Gliosis at 39

    An inflammatory response indicated by the presence of activated microglia and astrocytes begins around 9 months. The onset, distribution, and abundance of activated microglia and astrocytes correlate with Aβ deposition.

  3. X
    Cognitive Impairment at 35

    Age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze (Richards et al., 2003).

Absent
  • Tangles at

    Absent.

  • Changes in LTP/LTD at

    No difference in LTP in the dentate gyrus at 3 and 10 months compared to wild-type mice (Richards et al., 2003).

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN2 APP K670_M671delinsNL (Swedish), PSEN2 N141I APP: Transgenic; PSEN2: Transgenic Alzheimer's Disease

Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition.

Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze.

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PS/APP

Observed
  1. X
    Plaques at 26

    Large amounts of Aβ accumulate in the cerebral cortex and hippocampus, starting around 6 months and increasing with age. Other brain regions are affected later. Both diffuse and fibrillar plaques form (Gordon et al., 2002).

  2. X
    Neuronal Loss at 79

    Neuronal loss in the CA1 region of the hippocampus has been reported at 22 months accompanied by reduced glucose utilization (Sadowski et al., 2004).

  3. X
    Gliosis at 26

    GFAP-positive astrocytes appear first in the cortex in the vicinity of the developing Aβ deposits. Numbers increase with age, becoming confluent. Numbers of resting microglia (positive for complement receptor-3) increase in the vicinity of deposits at 6 months, but activated microglia (positive for MHC-II) are negligible before 12 months and more variable (Gordon et al., 2002).

  4. X
    Cognitive Impairment at 12

    Double and single transgenic mice had reduced spontaneous alternation performance in a “Y” maze, a test of spatial memory, at 12-14 weeks, before substantial Aβ deposition (Holcomb et al., 1998). Progressive age-related cognitive impairment is seen later in select tasks (e.g. water maze acquisition and radial arm water maze working memory)(Arendash et al., 2001).

Absent
  • Tangles at

    Neurofibrillary tangles are not associated with this model, but hyperphosphorylated tau is detected, starting at 24 weeks, appearing as punctate deposits near amyloid deposits in the cortex and hippocampus (Kurt et al., 2003).

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C) APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter,  cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation.

Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels.

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PS cDKO

Observed
  1. X
    Neuronal Loss at 9

    Significant increase (about 8-fold) in apoptotic neurons at 2 months of age, although the total number of cortical neurons is not significantly altered due to the low basal level of apoptosis in the cerebral cortex. By 4 months of age, the cumulative loss of cortical neurons reaches about 9 percent of all cortical neurons.

  2. X
    Gliosis at 17

    Astrogliosis and microgliosis; up-regulation of GFAP and other inflammatory markers are observed in the neocortex and hippocampus at 6 months, and this increases with age (Wines-Samuelson et al., 2010, Beglopoulos et al., 2004). 

  3. X
    Synaptic Loss at 26

    Reduction in synaptophysin immunoreactivity in hippocampal CA1 pyramidal neurons by 6 months. Reduction in dendritic spines by 9 months (Saura et al., 2004).

  4. X
    Cognitive Impairment at 9

    Deficits in the Morris water maze and contextual fear conditioning are mild at 2 months, but become more severe with age (Saura et al., 2004). 

Absent
  • Plaques at

    Absent.

  • Tangles at

    Tangles are absent, but hyperphosphorylation of tau has been reported in 9 month-old mice.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
PSEN1, PSEN2 PSEN1: Conditional Knock-out; PSEN2: Knock-Out Alzheimer's Disease

At 2 months the number of apoptotic neurons is elevated about 8-fold. By 6 months, about 18 percent of of cortical neurons are lost. Up-regulation of inflammatory markers and progressive astrogliosis and microgliosis in the neocortex and hippocampus.

Impairments in hippocampal learning and memory as indicated by Morris water maze and contextual fear conditioning evident by 2 months and worsens with age.

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Psen1 L435F knock-in

Observed
Absent
  • Plaques at

    No plaques at 15 days of age.

  • Neuronal Loss at

    No neuron loss at 15 days of age.

  • Gliosis at

    No astrogliosis or microgliosis at 15 days of age.

No Data
  • Tangles at

    No data. 

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Psen1, App PSEN1 L435F Psen1: Knock-In; App: Knock-In Alzheimer's Disease

None observed in 15-day-old rats.

Unknown.

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PWK.APP/PS1

Observed
  1. X
    Plaques at 32

    Thioflavin S-positive amyloid plaques are present in the cortex and CA1 region of the hippocampus by 8 months of age, with females having more plaques in the cortex than males.

  2. X
    Gliosis at 33

    Plaque-associated microgliosis observed by 8 months.

Absent
  • Tangles at

    Not observed.

  • Neuronal Loss at

    Not observed.

  • Cognitive Impairment at

    Working memory and short-term memory were intact at 7 to 8 months, as assessed by tests in the Y-maze.

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques and plaque-associated gliosis by 8 months.

Transgenic mice are hyperactive and aggressive. Working memory and short-term memory are intact at 7 to 8 months, as assessed by tests in the Y-maze.

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rTg9191

Observed
  1. X
    Plaques at 35

    Plaques emerge first in the cerebral cortex, starting around 8 months of age. This is followed by plaques in the hippocampus at 10.5 to 12.5 months of age. Some dense core plaques develop.

  2. X
    Neuronal Loss at 9

    Expression of the tetracycline transactivator (tTA) resulted in reduced forebrain weight and smaller dentate gyri in rTg9191 mice compared to non-Tg littermates. This effect was also observed in mice expressing tTA alone, and is thought to be a developmental effect, as it was observed even in young mice (e.g., 2-6 months of age).

  3. X
    Gliosis at 104

    rTg9191 mice develop reactive gliosis (astrocytosis and microgliosis) in the vicinity of dense-core plaques by 24 months of age.

Absent
  • Tangles at

    Tangles are not observed, but hyperphosphorylated tau develops with age.

  • Cognitive Impairment at

    No transgene-related deficits seen in Morris water maze (4, 12, 21, 24 months of age) or fixed consecutive number test (23 months of age).

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish), APP V717I (London) APP: Transgenic Alzheimer's Disease

Age-associated pathology in the cerebral cortex and hippocampus starting at 8 and 10½-12½ months of age, respectively. Gliosis and hyperphosphorylated tau in the vicinity of dense-core plaques. Fibrillar oligomeric species, e.g., Aβ dimers.

No transgene-related deficits seen in Morris water maze (4, 12, 21, 24, months of age) or fixed consecutive-number (23 months of age) tests.

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rTgTauEC

Observed
  1. X
    Tangles at 78

    By 18 months of age, Gallyas silver-positive staining is observed, indicative of paired helical filaments. This is followed by thioflavin-S staining at 24 months. Tau pathology develops first in neurons of the medial EC expressing human tau, followed by neurons in the dentate gyrus, CA1 and CA2/3(de Calignon et al., 2012).

  2. X
    Neuronal Loss at 83

    Neuronal loss is detectable by 24 months of age in areas with transgene expression (e.g. layer II of the EC and parasubiculum), compared with age-matched mice expressing only tTA. Significant neuronal loss was not observed at 21 months (de Calignon et al., 2012).

  3. X
    Gliosis at 104

    Microglial activation and astrogliosis by 24 months of age, in conjunction with axonal degeneration and neuronal loss (de Calignon et al., 2012).

  4. X
    Synaptic Loss at 104

    By 24 months of age pre- and post-synaptic densities were reduced in the middle third of the molecular layer of the dentate gyrus as measured by synapsin-1 and PSD-95 staining (de Calignon et al., 2012).

  5. X
    Changes in LTP/LTD at 70

    At 16 months of age, subtle differences in electrophysiological properties have been observed in the perforant pathway, including a decrease in LTP and an increase in the probability of neurotransmitter release (Polydoro et al., 2014).

  6. X
    Cognitive Impairment at 70

    Very mild and specific deficits in contextual fear conditioning at 16 months of age, but no deficits in the radial arm maze (Polydoro et al., 2014).

Absent
  • Plaques at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss.

Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test.

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rTg(tauP301L)4510

Observed
  1. X
    Tangles at 17

    Pretangles as early as 2.5 months. Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months.

  2. X
    Neuronal Loss at 24

    Decreased (~60%) CA1 hippocampal neurons by 5.5 months with significant loss in brain weight. Progressive loss of neurons and brain weight in 7 and 8.5 month mice with ~23% of CA1 pyramidal cells remaining at 8.5 months. Gross atrophy of the forebrain by 10 months.

  3. X
    Synaptic Loss at 35

    Significant loss of dendritic spines at 8-9 months (~30% decrease in spine density in somatosensory cortex).

  4. X
    Cognitive Impairment at 11

    Retention of spatial memory (Morris Water Maze) became impaired from 2.5 to 4 months. No significant motor impairments up to 6 months. Spatial memory improved when transgene suppressed by dox.

Absent
  • Plaques at

    Absent.

No Data
  • Changes in LTP/LTD at

    LTP at the Schaffer collateral-CA1 synapse is normal at 1.3 months, but impaired at 4.5 months.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60 percent) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (six to eight week) suppression of transgenic tau.

Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved.

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SHR24

Observed
  1. X
    Tangles at 38

    Argyrophilic neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem.

  2. X
    Synaptic Loss at 60

    Decreased levels of synaptophysin and a decreased number of synaptic vesicles per synapse in animals at the end of the lifespan of this line.

Absent
  • Neuronal Loss at

    No neuron loss was observed in the hippocampi or cortices of male rats examined at 15 month of age.

No Data
  • Plaques at

    No data.

  • Gliosis at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    Sensorimotor deficits and abnormal reflexes observed as early as 3.5 months, but no data available from cognitive tests.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT: Transgenic Alzheimer's Disease

Neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem, beginning at 9 to 10 months. No neuron loss was observed in the hippocampus or cortex.

SHR24 rats exhibit age-dependent impairments in several neurobehavioral tests; hind-limb clasping during the tail-hang test is one of the earliest abnormalities to appear, evident by 3.5 months of age.

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SHR318

Observed
  1. X
    Tangles at 38

    Argyrophilic neurofibrillary tangles are particularly prominent in the brainstem and spinal cord.

  2. X
    Cognitive Impairment at 18

    At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze.

Absent
  • Neuronal Loss at

    Neuron numbers in the hippocampi and brainstem gigantocellular reticular nucleus do not differ between 10.5-month SHR318 rats and non-transgenic rats.

No Data
  • Plaques at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT: Transgenic Alzheimer's Disease

Neurofibrillary tangles first appear at 9 months and are particularly prominent in the brainstem and spinal cord. Axonal degeneration is observed in the brainstem and spinal cord of 10- to 12-month animals.

At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze. Reflexes and sensorimotor coordination are impaired at 7 months.

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SHR72

Observed
  1. X
    Tangles at 30

    Neurofibrillary tangles, demonstrated by Gallyas silver stain, are present in the brainstem and spinal cord.

  2. X
    Gliosis at 29

    Astrogliosis and microgliosis are present in brainstem regions bearing neurofibrillary tangles.

Absent
  • Neuronal Loss at

    Although neuron loss has not been documented, chromatolytic neurons and damaged axons were seen in the brains of 7-month animals, particularly in the brainstem reticular formation.

No Data
  • Plaques at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    Sensorimotor deficits and abnormal reflexes observed as early as 3 months, but no data available from cognitive tests.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT: Transgenic Alzheimer's Disease

Neurofibrillary tangles, demonstrated by Gallyas silver stain, were found the brainstems and spinal cords of terminal stage (7- to 8-month old) animals. Chromatolytic neurons and damaged axons were also observed at this stage.

Sensorimotor deficits and loss of muscle strength are apparent at 3 months. This stage lasted about three months, and then rats experienced a rapid, dramatic decline in neurological function, succumbing within several days.

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SHRSP/FAD

Observed
  1. X
    Plaques at 69

    Diffuse amyloid plaques observed at 16-18 months, the only age examined to date.

  2. X
    Tangles at 70

    Occasional neurons appear to contain globose neurofibrillary tangles, as revealed by immunostaining using an antibody directed against tau phosphorylated at serine 422, an epitope found in paired helical filaments.

  3. X
    Gliosis at 71

    Hypertrophied microglia and elevated levels of GFAP observed at 16-18 months, the only age examined to date.

  4. X
    Cognitive Impairment at 72

    Working memory deficits as assessed by novel object recognition, but not as assessed by spontaneous alternation in the Y-maze, at 16-18 months, the only age examined to date.

Absent
  • Synaptic Loss at

    Levels of SNAP25, synaptophysin, and drebrin do not differ from non-hypertensive, non-transgenic rats at 16-18 months, the only age examined to date.

No Data
  • Neuronal Loss at

    A reduction in calbindin staining might reflect a loss of inhibitory neurons. Levels of caspase-cleaved actin, a marker of apoptosis, are elevated, compared with non-hypertensive, non-transgenic rats.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease, Vascular Dementia

Amyloid plaques, microgliosis, and possible astrogliosis. Occasional neurons appear to contain paired helical filament tau. Demyelination. Reduced calbindin immunoreactivity and increased levels of caspase-cleaved actin may indicate neuron loss.

Hyperactive. Working memory deficits as assessed by novel object recognition, but not as assessed by spontaneous alternation in the Y-maze.

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Snx1*D465N/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Snx1, APOE, Trem2 TREM2 R47H Snx1: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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Sorl1*A528T

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Sorl1 SORL1 A528T (SNP 13) Sorl1: Knock-In Alzheimer's Disease

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Sorl1*A528T/APOE4/Trem2*R47H

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Sorl1, APOE, Trem2 TREM2 R47H, SORL1 A528T (SNP 13), APOE C130R (ApoE4) Sorl1: Knock-In; APOE: Knock-In; Trem2: Knock-In Alzheimer's Disease

Unknown.

Unknown.

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SORL1 transgenic (Cre-inducible)

Observed
Absent
  • Changes in LTP/LTD at

    LTP at Schaffer collateral-CA synapses was similar in hippocampal slices from 3-month-old Rosa26Tg/+ and wild-type mice. The application of Aβ oligomers impaired LTP in slices from wild-type mice but did not affect LTP in SORL1 transgenic mice.

  • Cognitive Impairment at

    Three-month-old Rosa26Tg/+ SORL1 transgenic mice performed similarly to wild-type mice in the acquisition and retention phases of the Morris Water Maze test. Hippocampal injection of Aβ oligomers prevented wild-type mice from learning the location of the escape platform but did not affect the performance of the transgenic mice.

No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
SORL1 SORL1: Transgenic Alzheimer's Disease

Unknown.

Normal performance in the Morris Water Maze.

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SORLA-deficient

Observed
Absent
  • Plaques at

    No amyloid plaques observed up to 10 months of age. When SORLA-deficient mice are crossed with APP transgenic models of amyloidosis, amyloid deposition is accelerated, compared with the parental APP transgenic line.

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    Neuron loss was not seen in the substantia nigra and ventral tegmental areas, assessed at 5 weeks and 45 weeks. Data on neuron numbers are not available from other brain regions. Nigrostriatal connectivity appears to be disrupted in SORLA-deficient mice.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No differences in LTP were observed in hippocampal slices from 10- to 12-month-old Sorl1-/- mice and slices from littermates heterozygous for the Sorl1 deletion (Rohe et al., 2008). It is not known whether LTP in these genotypes differs from that of wild-type mice.

  • Cognitive Impairment at

    Compared with wild-type mice, SORLA-deficient mice exhibited more arm entries and more time spent in the open arms of the elevated plus maze—behaviors interpreted as evidence of hyperactivity and reduced anxiety. Hyperactivity was also noticed in the open field test.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Sorl1 Sorl1: Knock-Out Alzheimer's Disease

Mice do not generate amyloid plaques. Disrupted nigrostriatal connectivity and thinner inner nuclear layer of the retina.

Hyperactivity and reduced anxiety, compared with wild-type mice.

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TAS10 (thy1-APPswe)

Observed
  1. X
    Plaques at 52

    Fibrillar amyloid plaques develop by 12 months in the cortex and hippocampus.

  2. X
    Gliosis at 26

    Astrogliosis and microgliosis underway by 6 months of age in the dentate gyrus.

  3. X
    Synaptic Loss at 104

    TAS10 mice initially have more synapses than non-Tg mice; specifically, greater numbers of synapses per neuron were documented at 12 and 18 months of age. However, by 24 months of age, TAS10 mice have fewer synapses than non-Tg mice.

  4. X
    Cognitive Impairment at 26

    Deficits in spatial learning present by 6 months of age as measured by the Morris water maze. No difference from non-Tg at 2 months of age. Deficits in Y maze at 12 months. No deficit in fear conditioning up to 24 months of age.

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Qualitative difference in neuronal numbers at 24 months in specific regions of the hippocampus, but no significant neuronal loss.

  • Changes in LTP/LTD at

    At 12 to 14 months of age, deficits in basal synaptic transmission have been observed in the CA1 region, but short- and long-term synaptic plasticity are relatively normal (Brown et al., 2005).

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish) APP: Transgenic Alzheimer's Disease

Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes.

Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning.

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