Research Models

Selected Results

65 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 (60)
3xTg-AD, The LaFerla mouse B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax C7BL/6;129X1/SvJ;129S1/Sv APP, PSEN1, MAPT APP KM670/671NL (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. APP: Transgenic; PSEN1: 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
5XFAD, APP/PS1, Tg6799, Tg-5xFAD B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax C57BL/6 x SJL APP, PSEN1 APP KM670/671NL (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. Research with this model is available from QPS Austria. Oakley et al., 2006 Yes
5XFAD, APP/PS1, Tg6799, Tg-5xFAD B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax C57BL6 APP, PSEN1 APP KM670/671NL (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 Jawhar et al., 2012, Richard et al., 2015 Yes
C57BL/6J APP APP KM670/671NL (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
B6-Tg/Thy1APP23Sdz B6.Cg-Tg(Thy1-APP)3Somm/J C57BL/6 APP APP KM670/671NL (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
APP(SL)PS1KI, APPxPS1-Ki, APPSL/PS1KI, APP(SL)/PS1(KI), APP/PS1KI The PS1KI line was established in 129SV and backcrossed >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 KM670/671NL (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
happ-SL x hTau, APP751-SL x TAU441 V337M R406W C57BL/6 x DBA MAPT, APP APP KM670/671NL (Swedish), APP V717I (London), MAPT V337M (Seattle), MAPT R406W Cross of two models from QPS: (1) APP751SL, which overexpresses mutant human APP (isoform 751) with the Swedish (K670N/M671L) and London (V717I) mutations under the control of the brain-specific Thy1 promoter, and (2) THMT, which overexpresses human MAPT (441) with the V337M and R406W mutations under the control of Thy1. MAPT: Transgenic; APP: Transgenic Alzheimer's Disease Plaques start at 3-6 months. Some acceleration of amyloid deposition in the amygdala as compared to the hAPPSL single transgenic; detected in bigenic animals by 3 months vs 6 months. Cognitive impairment at 3 months demonstrated by the Morris Water Maze. Eyes appear smaller compared to wild-type mice, but pupillary reflex, eye blink reflex, and visual test performance are normal. QPS-Austria Yes
APP KI, line ADF Apptm1Sud/J Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl<+>; C57BL/6 and maintained on a mixed background APP APP KM670/671NL (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
APPNL-F/NL-F Apptm2.1Tcs/Apptm2.1Tcs C57BL/6 APP APP KM670/671NL (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
APPNL-G-F/NL-G-F, AppNL-G-F Apptm3.1Tcs/Apptm3.1Tcs C57BL/6 APP APP KM670/671NL (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
APPPS1-21 B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr C57BL/6J APP, PSEN1 APP KM670/671NL (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
APPswe/PSEN1dE9/MAPT, APPswe/PSEN1dE9/CaMKIIa-tTa/TRE-Tg21221 B6.C3 x B6.129 x FVB APP, PSEN1, MAPT APP KM670/671NL (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: Knock-In 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
C57Bl/6xDBA APP APP KM670/671NL (Swedish), APP V717I (London) These mice are the results of cross-breeding APPSL mice (human APP751 with Swedish (K670M/N671L) and London (V717I) mutation under control of the Thy-1 promoter) and hQC mice (human glutaminyl cyclase under control of the Thy-1 promoter). APP: Transgenic Alzheimer's Disease Increased pGlu Aβ in cortex and hippocampus starting at 7.5 months. Increased ThioflavinS and 6E10 positive plaques in cortex and hippocampus starting at 5.5 months. Increased microgliosis and astrocytosis in cortex and hippocampus starting at 7.5 months. Spatial memory deficits starting at 4 months (Morris water maze). At 9 months deficits in contextual fear conditioning. At 12 months animals are less anxious (elevated plus maze). QPS-Austria; livestock. Contact: office-austria@qps.com No
Tg2576;Pdgfrβ+/- APPsw mice on C57BL/6; Pdgfrβ+/- mice on 129S1/SvlmJ. APP, PDGFRB APP KM670/671NL (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
APPSwDI/NOS2 bigenic mice, APPSDI/NOS2KO, CVN B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax C57BL/6J; C57BL/6N APP, NOS2 APP KM670/671NL (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
APPSw, hAPPSwe (line 71) , hAPPSwe (line 72), huAPPSw B6.D2-Tg(Thy1-APPSwe)71Blt; B6.D2-Tg(Thy1-APPSwe)72Blt C57BL/6, DBA/2, crossed to C57BL/6 APP APP KM670/671NL (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
R1.40, APPK670/M671, R1.40-YAC B6.129-Tg(APPSw)40Btla/Mmjax (129X1/SvJ x 129S1/Sv)F1-Kitl<+> APP APP KM670/671NL (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
APP(695)Swe C3B6-Tg(APP695)3Dbo/Mmjax C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J APP APP KM670/671NL (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 KM670/671NL (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
APP YAC Swe/Lon (line J1.96), B6-J1-96 B6.129S4-Tg(APPSwLon)96Btla/Mmjax 129S4/SvJae-derived J1 ES cells; backcrossed to C57BL/6 APP APP KM670/671NL (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
APPSwe (line C3-3)/PSEN1(A246E)(line N-5), APP/PS1, APPswe + PS1 (A246E), APP + PS1, AP mouse, C3-3/N-5 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/Mmjax Origin: (C57BL/6J x C3H/HeJ)F2 APP, PSEN1 APP KM670/671NL (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
APPSwe(line C3-3) X PS1dE9 (line S-9), C3-3/PS1-dE9, C3-3 x S-9 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 KM670/671NL (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
APP/PS1, APPswe/PS1deltaE9, line 85, APP(swe) + PSEN1DeltaE9, APdE9, Borchelt mice B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax C57BL/6 x C3H)F2 APP, PSEN1 APP KM670/671NL (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
NSE-APPsw Origin: C57BL/6 x DBA/2 APP APP KM670/671NL (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
APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line Inbred C57BL/6 APP APP KM670/671NL (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 KM670/671NL (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 KM670/671NL (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
BACE1fl/fl/UbcCreER X 5xFAD C57BL/6J Bace1, APP, PSEN1 APP KM670/671NL (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
APOE2-FAD, APOE2 Targeted Replacement x 5xFAD C57BL/6 APOE, APP, PSEN1 APP KM670/671NL (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
APOE3-FAD, APOE3 Targeted Replacement x 5xFAD C57BL/6 APOE, APP, PSEN1 APP KM670/671NL (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
APOE4-FAD, APOE4 Targeted Replacement x 5xFAD C57BL/6 APOE, APP, PSEN1 APP KM670/671NL (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
PDGF-APPSw,Ind, PDGF-hAPP695,751,770V171F, KM670/671NL, hAPPJ20, hAPP, Mucke mice B6.Cg-Zbtb20Tg(PDGFB-APPSwInd)20Lms/2Mmjax C57BL/6 APP APP KM670/671NL (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
TASD41, Line 41, hAPPSL, hAPP-SL, AβPP751, mThy1-hAβPP751 Swe Lon (line 41), APP751SL, hAPPlon/swe line 41, APP41 mThy1-hAβPP751 Swe Lon C57BL/6 x DBA APP APP KM670/671NL (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
APP(Swedish,Indiana), line J9, hAPPJ9, hAPPlow C57BL/6 APP APP KM670/671NL (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
hAPP/hTau/hPS1, PLB1(Triple) C57BL6 APP, MAPT, PSEN1 APP V717I (London), APP KM670/671NL (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
B6.PS2APP, TG B6.PS2APP mice (line B6.152H) Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz C57BL/6 APP, PSEN2 APP KM670/671NL (Swedish), PSEN2 N141I (Volga German) 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 KM670/671NL (Swedish), PSEN2 N141I (Volga German) 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
PS1 + APP, PSAPP, APP/PS1, APP/PS1 double transgenic B6/D2/Swe/SJL mixed background APP, PSEN1 APP KM670/671NL (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
APPNLI 129S6FVB F1 APP APP KM670/671NL (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
thy1-APPswe Transgene injected into C57BL/6 x C3H oocytes, some backcrossing to C57BL/6 APP APP KM670/671NL (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
TAS10 x TPM, APPswe x PS1.M1466V, TAS/TPM 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 KM670/671NL (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
Triple transgenic, 3Tg B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L) C57BL/6, DBA/2; backcrossed to C57BL/6 APP, MAPT, PSEN2 APP KM670/671NL (Swedish), MAPT P301L, PSEN2 N141I (Volga German) 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
line 102 B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (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
line 107 B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (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
line 885 B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (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
Hsiao mice, App-Swe, App-sw, APP(sw), APPSwe B6;SJL-Tg(APPSWE)2576Kha B6;SJL Mixed Background APP APP KM670/671NL (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 and Charles River.  The CRO PsychoGenics offers research services with this line. Hsiao et al., 1996 Yes
APPSwe-Tau, APPSwe(2576)/TauJNPL3, TAPP Tg(APPSWE)2576Kha; Tg(Prnp-MAPT*P301L)JNPL3Hlmc C57BL/6, DBA/2, SJL, SW Mixed Background APP, MAPT APP KM670/671NL (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
Tg-Swe C57BL/6J APP APP KM670/671NL (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 KM670/671NL (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
tg ArcSwe, APP-ArcSwe C57BL/6J APP APP KM670/671NL (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 Lars Nilsson Lord et al., 2006 Yes
APP(swe/ind) CRND8 Hybrid C3H/He-C57BL/6 APP APP KM670/671NL (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
mAPP/DN-RAGE, APP/DN-RAGE C57BL/6 APP, RAGE (AGER) APP KM670/671NL (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 KM670/671NL (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
APP-Swedish,Dutch,Iowa, APPSwDI C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax C57BL/6 APP APP KM670/671NL (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
BAC-TREM2 X 5xFAD TREM2-BAC: FVB/NJ; 5xFAD: C57BL/6 X SJL TREM2, APP, PSEN1 APP KM670/671NL (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
CV+mTrem2−/−5XFAD C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 Trem2, TREM2, APP, PSEN1 APP KM670/671NL (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
R47H+mTrem2−/−5XFAD C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 Trem2, TREM2, APP, PSEN1 TREM2 R47H, APP KM670/671NL (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
Trem2-/-5XFAD, mTrem2-/-5XFAD  C57BL/6 -TREM2tm1cln; B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmja C57BL/6 Trem2, APP, PSEN1 APP KM670/671NL (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
APPPS1;Trem2-/- TREM2tm1(KOMP)Vlcg; B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr C57BL/6 Trem2, APP, PSEN1 APP KM670/671NL (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
APPPS1-21;Trem2+/R47H C57BL6/J Trem2, APP, PSEN1 TREM2 R47H, APP KM670/671NL (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
Rat Models (5)
AgenT Wistar APP, PSEN1 APP KM670/671NL (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 KM670/671NL (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
Fischer 344 APP, PSEN1 APP KM670/671NL (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. Agca et al., 2016, Klakotskaia et al., 2018 Yes
HsdBrl:WH Wistar APP APP KM670/671NL (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
Fischer 344 APP, PSEN1 APP KM670/671NL (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

52 Visualizations

AD-related Research Models

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
APP, PSEN1, MAPT APP KM670/671NL (Swedish), MAPT P301L, PSEN1 M146V APP: Transgenic; PSEN1: 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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (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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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 KM670/671NL (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 KM670/671NL (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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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 KM670/671NL (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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APP751-SL x THMT

Observed
  1. X
    Plaques at 13

    Plaques start at 3 months in the frontal cortex and become more widespread with age.

  2. X
    Gliosis at 26

    Microglial activation. Numerous glial cells around amyloid plaques at 6 months.

  3. X
    Cognitive Impairment at 13

    Cognitive impairment at 3 months demonstrated by Morris Water Maze.

Absent
No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, APP APP KM670/671NL (Swedish), APP V717I (London), MAPT V337M (Seattle), MAPT R406W MAPT: Transgenic; APP: Transgenic Alzheimer's Disease

Plaques start at 3-6 months. Some acceleration of amyloid deposition in the amygdala as compared to the hAPPSL single transgenic; detected in bigenic animals by 3 months vs 6 months.

Cognitive impairment at 3 months demonstrated by the Morris Water Maze.

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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 KM670/671NL (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 KM670/671NL (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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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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (Swedish), PSEN1: deltaE9 APP: Transgenic; PSEN1: Transgenic; MAPT: Knock-In 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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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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (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 (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 KM670/671NL (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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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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (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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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 KM670/671NL (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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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 KM670/671NL (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 KM670/671NL (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 KM670/671NL (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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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 KM670/671NL (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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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 KM670/671NL (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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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 KM670/671NL (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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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 KM670/671NL (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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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 KM670/671NL (Swedish), PSEN2 N141I (Volga German) 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 KM670/671NL (Swedish), PSEN2 N141I (Volga German) 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 KM670/671NL (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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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 KM670/671NL (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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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 KM670/671NL (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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TASTPM (TAS10 x TPM)

Observed
  1. X
    Plaques at 26

    Aβ begins to deposit at 3 months of age, with fibrillar plaques evident by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid is also observed. Plaque pathology is more severe in female mice.

  2. X
    Gliosis at 28

    Greater numbers of reactive astrocytes and microglia by 6 months of age in the hippocampus and cortex, predominantly near amyloid plaques.

  3. X
    Cognitive Impairment at 26

    Age-dependent impairment in object recognition memory starting around 6 months of age for both sexes. No impairment at 3 to 4 months of age.

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Minimal neuronal loss up to 10 months of age. Some signs of loss in the immediate vicinity of plaques in the hippocampus (Howlett et al., 2008).

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 M146V 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. 

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TauPS2APP

Observed
  1. X
    Plaques at 17

    Rare amyloid plaques at 4 months, plaques become more abundant with age. By 8 months the number of amyloid plaques increases considerably in the subiculum and the CA1 region of the hippocampus (Grueninger et al., 2010).

  2. X
    Tangles at 70

    Abnormally phosphorylated tau is detectable at 4 months in both TauPS2APP and tau single transgenic mice especially in the subiculum, amygdala, and the CA1 region of the hippocampus. Tau pathology increases with age with numerous tangle-like deposits in the hippocampus confirmed by Gallyas silver staining at 16 months (Grueninger et al., 2010).

  3. X
    Cognitive Impairment at 17

    Impairment is not age-associated and does not progress from age 4 months to 12 months (Grueninger et al., 2010).

Absent
  • Neuronal Loss at

    No overt neuronal loss in the hippocampus at 16 months (Grueninger et al., 2010).

No Data
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, MAPT, PSEN2 APP KM670/671NL (Swedish), MAPT P301L, PSEN2 N141I (Volga German) 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.

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Tg2576

Observed
  1. X
    Plaques at 48

    Numerous parenchymal Aβ plaques by 11-13 months.

  2. X
    Gliosis at 43

    Increase in microglial density and size in plaque-forming areas of the brain including the hippocampus, frontal cortex, entorhinal cortex, and occipital cortex in 10-16 month old hemizygotes (Frautschy et al., 1998).

  3. X
    Synaptic Loss at 20

    Dendritic spine loss by 4.5 months In the CA1 region of the hippocampus (Lanz et al., 2003).

  4. X
    Changes in LTP/LTD at 22

    By 5 months, there was a decline in LTP in the dentate gyrus after perforant path stimulation compared to wild-type; impairment was not observed at 2 months (Jacobsen et al., 2006). Both the CA1 and dentate gyrus of aged mice (>15 months) are impaired (Chapman et al., 1999). Differences have been observed between the Schaffer collateral and mossy fiber pathways (Jung et al., 2011).

  5. X
    Cognitive Impairment at 26

    Impaired spatial learning, working memory, and contextual fear conditioning at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months.

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent or very limited.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish) 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.

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Tg2576/Tau(P301L) (APPSwe-Tau)

Observed
  1. X
    Plaques at 39

    Plaques develop gradually with age. No plaques at 5 months. Very few small plaques at 6 and 7 months. By 9 months plaques scattered throughout the cortex, hippocampus and amygdala, continue to increase at 12 months. Similar distribution as Tg2576.

  2. X
    Tangles at 13

    Neurofibrillary tangles in the spinal cord and pons as early as 3 months, but more consistent and numerous by 6 months. Tangles morphologically similar to those in JNPL3 mice but older bigenic female mice had a marked increase in neurofibrillary tangles in limbic areas by 6 months, especially the olfactory cortex, entorhinal cortex and amygdala (Lewis et al., 2001).

  3. X
    Gliosis at 13

    Reactive astrocytes and microglia as early as 3 months in the hippocampus as measured by GFAP and CD45. Increased astrocytosis with age especially in limbic areas with the most neurofibrillary tangles. Microglia especially concentrated around plaques at 9 and 12 months (Lewis et al., 2001).

Absent
No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, MAPT APP KM670/671NL (Swedish), MAPT P301L 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.

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tg-APPSwe

Observed
  1. X
    Plaques at 52

    Plaques are detectable at approximately 12 months and are heterogeneous in morphological structure and size, as well as in terms of fluorescence emitted when stained with luminescent polymers (conformational amyloid ligands)(Philipsson et al., 2009).

  2. X
    Gliosis at 52

    Microgliosis and astrogliosis are most prominent in the hippocampus, but also found locally around deposits in the cerebral cortex and in thalamus at approximately 12 months (Philipsson et al., 2009).

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish) 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.

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Tg-ArcSwe

Observed
  1. X
    Plaques at 22

    Extracellular amyloid plaque deposition starts at around 5-6 months of age (Lord et al., 2006) and is most consistently present in the cerebral cortex, hippocampus, and thalamus (Lillehaug et al., 2013).

  2. X
    Gliosis at 26

    Microgliosis and astrogliosis most prominent in the hippocampus, but also locally around deposits in the cerebral cortex and thalamus.

  3. X
    Cognitive Impairment at 17

    Transgene-dependent spatial learning impairment in the Morris water maze (4-8 months) (Lord et al., 2009) and in an Intellicage-based Passive Avoidance test (16 months)(Codita et al., 2010).

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
APP APP KM670/671NL (Swedish), APP E693G (Arctic) 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.

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TgCRND8

Observed
  1. X
    Plaques at 13

    Amyloid deposition progresses with age. Thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques appear first in the subiculum, amygdala and frontal cortex, spread to the dentate gyrus, the olfactory bulb, and later thalamus, cerebral vasculature, and striatum, followed by the cerebellum and brain stem (Chishti et al., 2001).

  2. X
    Neuronal Loss at 26

    Variable cell loss by region. No difference in overall cell count, but fewer hippocampal neurons at 6 months (Brautigam et al., 2012).

  3. X
    Gliosis at 13

    Microglia activation appears simultaneously with Aβ deposition, with only rare activated microglia at 9-10 weeks, but by 13-14 weeks microglia cluster around Aβ deposits in the cerebral cortex and hippocampus; numerous by 20 weeks. Robust astrogliosis slightly later with clusters of GFAP+ astrocytes emerging around plaques at 13-14 weeks (Dudal et al., 2004).

  4. X
    Synaptic Loss at 26

    Reduced synaptophysin immunoreactivity in the vicinity of plaques at 6 months (Adalbert et al., 2009).

  5. X
    Changes in LTP/LTD at 26

    In hippocampal slices from 6- to 12-month-old mice basal excitatory synaptic transmission (as assessed by I/O relationships) and LTP at CA1 are reduced in TgCRND8 mice compared with wild-type mice (Kimura et al., 2012).

  6. X
    Cognitive Impairment at 13

    Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze, present by 3 months (Chishti et al., 2001).

Absent
  • Tangles at

    Neurofibrillary tangles are absent (Chishti et al., 2001). Tau is hyperphosphorylated, nitrosylated and aggregated at 7-12 months especially in the neocortex, dentate gyrus, and the CA1 and CA3 areas of the hippocampus (Bellucci et al., 2007).

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP V717F (Indiana) 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.

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TgF344-AD

Observed
  1. X
    Plaques at 24

    Age-dependent accumulation of amyloid plaques in hippocampus and cortex between 6 and 26 months of age.

  2. X
    Tangles at 64

    Structures similar in appearance to neurofibrillary tangles revealed by Gallyas staining and immunostaining using an antibody directed against phospo-tau.

  3. X
    Neuronal Loss at 64

    Approximate 40 percent loss of neurons in hippocampus and cortex by 16 months.

  4. X
    Gliosis at 23

    Microgliosis and astrogliosis are apparent by 6 months.

  5. X
    Cognitive Impairment at 25

    Deficits in reversal learning in the Morris water maze apparent by 6 months.

Absent
No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1: deltaE9 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.

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Tg-SwDI (APP-Swedish,Dutch,Iowa)

Observed
  1. X
    Plaques at 13

    Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Amyloid-β deposits in the subiculum, hippocampus, and cortex at ~3 months. By ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (Davis et al., 2004).

  2. X
    Gliosis at 26

    Pronounced increase in the number of GFAP-positive astrocytes and activated microglia with age (6-24 months) especially in the thalamus and subiculum and to a lesser extent in the cortex (Miao et al., 2005).

  3. X
    Cognitive Impairment at 13

    Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months; beginning at 3 months took longer to find the escape hole. No difference in mobility, strength or coordination (Xu et al., 2007).

Absent
  • Tangles at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) 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.

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TREM2-BAC X 5xFAD

Observed
  1. X
    Plaques at 28

    Observed at 7 months, the youngest age examined.

  2. X
    Gliosis at 28

    Microgliosis observed; however, fewer plaque-associated microglia and altered microglial morphology (more ramified processes) compared with 5xFAD at 7 months, the only age examined.

Absent
  • Cognitive Impairment at

    5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired.

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
TREM2, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 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.

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TREM2, humanized (common variant) X 5XFAD

Observed
  1. X
    Plaques at 34

    Plaques observed in 8.5-month-old mice, only age reported thus far.

  2. X
    Gliosis at 34

    Microgliosis observed in 8.5-month-old mice, only age reported thus far.

Absent
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
Trem2, TREM2, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques surrounded by activated microglia.

No data.

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TREM2, humanized (R47H) X 5XFAD

Observed
  1. X
    Plaques at 34

    Plaques observed in 8.5-month-old mice, the only age reported thus far.

  2. X
    Gliosis at 34

    Microgliosis observed in 8.5-month-old mice, the only age reported thus far. Fewer plaque-associated microglia in mice expressing the R47H variant, compared with the common variant of human TREM2.

Absent
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
Trem2, TREM2, APP, PSEN1 TREM2 R47H, APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 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.

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Trem2 KO (Colonna) x 5XFAD

Observed
  1. X
    Plaques at 16

    Plaques present by 4 months, the earliest age studied.

  2. X
    Neuronal Loss at 32

    Loss of cortical layer V neurons by 8 months, the earliest age studied.

  3. X
    Gliosis at 16

    MIcrogliosis by 4 months, the earliest age studied.

Absent
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
Trem2, APP, PSEN1 APP KM670/671NL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 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.

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Trem2 KO (KOMP) x APPPS1

Observed
  1. X
    Plaques at 9

    Plaques are observed by 2 months.

  2. X
    Gliosis at 9

    Gliosis is observed by 2 months.

Absent
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
Trem2, APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 L166P 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.

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Trem2 R47H KI (Lamb/Landreth) X APPPS1-21

Observed
  1. X
    Plaques at 16

    Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, compared with APPPS1-21 mice homozygous for wild-type Trem2.

  2. X
    Gliosis at 16

    Fewer plaque-associated myeloid cells in APPPS1-21;Trem2+/R47H, compared with APPPS1-21 mice homozygous for wild-type Trem2.

Absent
  • Tangles at

    Tangles were not observed at 4 months of age, but hyperphosphorylated tau was detected in dystrophic neurites surrounding plaques.

  • Neuronal Loss at

    No differences in neuron number in cotical layer V in APPPS1-21;Trem2+/R47H mice relative to APPPS1-21 mice homozygous for wild-type Trem2, at 4 months of age.

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, APP, PSEN1 TREM2 R47H, APP KM670/671NL (Swedish), PSEN1 L166P 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.

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