Research Models
Selected Results
52 Models
Name | Other Names | Strain Name | Genetic Background | Gene | Mutation | Modification Info | Modification | Disease | Neuropathology | Behavior/Cognition | Other Phenotype | Availability | Primary Paper | Visualization | |
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Mouse Models (52) |
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3xTg-AD, The LaFerla mouse | B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax | C7BL/6;129X1/SvJ;129S1/Sv | Psen1, APP, MAPT | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V | Single-cell embryos from mice with knock-in of PSEN1 with the PS1M146V mutation were injected with two human transgenes (APP with the Swedish mutation and MAPT with the P30IL mutation). Transgenes integrated at a single locus under the control of the mouse Thy1.2 promoter. | Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic | Alzheimer's Disease | Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. | Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task. | The Jackson Lab; available through the JAX MMRRC Stock# 034830; Live | Oddo et al., 2003 | Yes | |||
5XFAD, APP/PS1, Tg6799, Tg-5xFAD | B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax | C57BL/6 x SJL | APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Two transgenes: mutant human APP with the APP Swedish, Florida, and London mutations and containing the 5' untranslated region driven by the mouse Thy1 promoter; and mutant human PSEN1 including the M146L and L286V mutations driven by the mouse Thy1 promoter. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles. | Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype. | The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live. | Oakley et al., 2006 | Yes | |||
C57BL/6J | APP | APP K670_M671delinsNL (Swedish), APP T714I (Austrian) | Transgene-expressing mutant APP with the Swedish mutation (K670N/M671L) and the Austrian mutation (T714I) under the control of the Thy1.2 promoter. | APP: Transgenic | Alzheimer's Disease | Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months. | Unknown. | Optogenetic stimulation induced epileptic seizures. | Unknown | Yamada et al., 2009 | Yes | ||||
B6-Tg/Thy1APP23Sdz | B6.Cg-Tg(Thy1-APP)3Somm/J | C57BL/6 | APP | APP K670_M671delinsNL (Swedish) | Transgene containing human APP (isoform 751) containing the Swedish (KM670/671NL) mutation under the murine Thy1 promoter. | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages. | Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages. | Hyperactivity observed between the ages of 6 weeks to 6 months. It is not known whether this persists or resolves in older animals. Abnormalities in open field test and impaired performance on rotorod observed from 3 months. | Available through The Jackson Laboratory Stock# 030504, Live | Sturchler-Pierrat et al., 1997 | Yes | ||
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 K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P | This animal is a cross between a PSEN1 knock-in line and an APP over-expressing line. The PS1 knock-in line was generated by introducing two point mutations in the wild-type mouse PSEN1, corresponding to the mutations M233T and L235P. APP751SL overexpresses human APP751 carrying the London (V717I) and Swedish (K670N/M671L) mutations under the control of the Thy1 promoter. | APP: Transgenic; PSEN1: Knock-In | Alzheimer's Disease | Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons. | Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates. | Viable and fertile. 6 month-old animals develop decreases in body weight, and a spinal deformity (kyphosis) is common. Impaired neurogenesis. | Available through Thomas Bayer or Benoit Delatour | Casas et al., 2004 | Yes | |||
happ-SL x hTau, APP751-SL x TAU441 V337M R406W | C57BL/6 x DBA | MAPT, APP | APP K670_M671delinsNL (Swedish), APP V717I (London), MAPT V337M, 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 K670_M671delinsNL (Swedish), APP V717I (London), APP E693Q (Dutch) | Knock-in of wild-type mouse APP exon 16 (truncated after residue KM), FLAG tag (2 repeats), a stop codon, a poly A signal region from the human growth hormone gene and an additional copy of exon 16 carrying the Swedish mutation and a modified exon 17 with the London and Dutch mutations. | APP: Knock-In | Alzheimer's Disease | Unknown. | Unknown. | The Jackson Lab: Stock# 008390; Cryopreserved | The Jackson Laboratory | No | |||
APPNL-F/NL-F | Apptm2.1Tcs/Apptm2.1Tcs | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP I716F (Iberian) | Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and the Swedish and Beyreuther/Iberian mutations. | APP: Knock-In | Alzheimer's Disease | Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. | Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. | No overexpression of APP. Generates wild-type levels of AICD. | Available through Takaomi Saido | Saito et al., 2014 | Yes | ||
APPNL-G-F/NL-G-F, AppNL-G-F | Apptm3.1Tcs/Apptm3.1Tcs | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) | Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and three pathogenic mutations (Swedish, Beyreuther/Iberian, and Arctic). | APP: Knock-In | Alzheimer's Disease | Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. | Memory impairment by 6 months as measured by the Y maze. | No overexpression of APP. Wild-type levels of AICD. | Available through Takaomi Saido | Saito et al., 2014 | Yes | ||
APPPS1-21, APP/PS1 | B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr | C57BL/6J | APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 L166P | Human transgenes APP KM670/671NL and PSEN1 L166P, both under the control of the Thy1 promoter. Integration site is on lower arm of chromosome 2 between 40 and 60 cm. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen. | Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months. | Aβ42 concentration in CSF decreases with age, with a 50% reduction by 6 months and an 80% reduction by 18 months. Aβ40 concentration also decreases, but less robustly (45% by 18 months). CSF concentration of total tau increases, starting at 6 months, and reaches a 5-fold increase by 18 months. | Available through Mathias Jucker | Radde et al., 2006 | Yes | ||
APPswe/PSEN1dE9/MAPT, APPswe/PSEN1dE9/CaMKIIa-tTa/TRE-Tg21221 | B6.C3 x B6.129 x FVB | APP, PSEN1, MAPT | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | APPswe/PSEN1dE9 mice were crossed with B6.129-Tg(CK-tTa) mice where the CaMKIIa promotor drives expression of tetracycline transactivator (tTA) in forebrain neurons. Offsping were then crossed to the Tg21221 line with a responder transgene of wildtype human tau. | APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic | Alzheimer's Disease | Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed. | No data. | N/A | APPswe/PSEN1dE9 mice available through JAX MMRRC Stock# 034829. | Jackson et al., 2016 | Yes | |||
C57Bl/6xDBA | APP | APP K670_M671delinsNL (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 K670_M671delinsNL (Swedish) | Progeny of APPsw transgenics (Tg2576) crossed with pericyte-deficient mice. Tg2576 express human APP with the Swedish double mutation driven by the hamster prion promoter. Pericyte-deficient mice were made by disrupting the Pdgfrβ gene using a PGKneobpA expression cassette to replace a 1.8 kb genomic segment spanning the signal peptide to the second immunoglobulin domain of PDGFRβ. | APP: Transgenic; PDGFRB: Knock-Out | Alzheimer's Disease | Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus. | Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition. | Progressive loss of pericytes due to reduced Pdgfrβ signaling. Early and progressive blood brain barrier breakdown, indicated by cerebral accumulation of IgG. Reduced microvascular circulation, indicated by reduced capillary length. | Available through Berislav Zlokovic | Sagare et al., 2013 | Yes | |||
APPSwDI/NOS2 bigenic mice, APPSDI/NOS2KO, CVN | B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax | C57BL/6J; C57BL/6N | APP, NOS2 | APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) | APPSwDI x NOS2 knockout animals. APPSwDI transgene expresses APP (isoform 770) with Swedish, Dutch, and Iowa mutations under the control of the mouse Thy1 promoter. NOS2 was disrupted by homologous recombination. The calmodulin binding domain of NOS2 was replaced by the neomycin resistance gene and the reading frame disrupted. | APP: Transgenic; NOS2: Knock-Out | Alzheimer's Disease | Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone. | Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks. | Decreased neuropeptide Y staining throughout the hippocampus, particularly in the CA3 region and subiculum. | The Jackson Lab; available through the JAX MMRRC Stock# 034849; Cryopreserved. Charles River: CVN mouse | Colton et al., 2008, Wilcock et al., 2008 | Yes | ||
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 K670_M671delinsNL (Swedish) | Transgene with human APP751 with the Swedish mutation driven by the Thy1.2 promoter. | APP: Transgenic | Alzheimer's Disease | Amyloid plaques by 17-18 months in the neocortex and hippocampus with detection of 5-10 fold more Aβ40 than Aβ42. Plaque burden significantly lower than in the double transgenic PS2APP. Lower levels of insoluble Aβ40 and Aβ42 than the PS2APP mouse at 16-18 months. | Unknown. | Available through Laurence Ozmen | Richards et al., 2003 | No | |||
R1.40, APPK670/M671, R1.40-YAC | B6.129-Tg(APPSw)40Btla/Mmjax | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | APP | APP K670_M671delinsNL (Swedish) | A 650 kb YAC transgene containing the entire human APP gene and ~250 kb of flanking sequence was mutated to include the Swedish mutation (K670N/M671L). Founder animals (line R1.40) were backcrossed to C57BL/6J. | APP: Transgenic | Alzheimer's Disease | By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months. | Unknown. | Increased mortality in young homozygous animals, especially females. At 3-4 months mice maintained on the C57BL/6J background exhibit spontaneous seizure-like activity as measured by EEG and are more susceptible to kainic acid-induced seizures. | The Jackson Lab; available through the JAX MMRRC Stock# 034831; Cryopreserved | Lamb et al., 1997 | Yes | ||
APP(695)Swe | C3B6-Tg(APP695)3Dbo/Mmjax | C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J | APP | APP K670_M671delinsNL (Swedish) | Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain and the Swedish mutation under the control of the mouse prion protein promoter. | APP: Transgenic | Alzheimer's Disease | Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age. | Congenic animals showed normal reference and working memory up to 12-14 months. | The Jackson Lab; available through the JAX MMRRC Stock# 034828; Cryopreserved | Borchelt et al., 1996, Savonenko et al., 2003 | Yes | |||
B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/Mmjax | C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J | APP | APP K670_M671delinsNL (Swedish) | Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain carrying the Swedish mutation under the control of the mouse prion protein promoter. | APP: Transgenic | Alzheimer's Disease | Age-dependent increase in Aβ42, with low levels at 6-14 months and high levels at 24-26 months. | No cognitive impairment in tasks of reference or working memory at 12-14 months. | More than half of the female hemizygous mice do not survive past 15 months of age. | The Jackson Lab; available through the JAX MMRRC Stock# 034835; Cryopreserved | Savonenko et al., 2003, Borchelt et al., 1996 | No | |||
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 K670_M671delinsNL (Swedish), APP V717I (London) | A 650 kb YAC transgene containing the entire human APP gene carrying the Swedish and London mutations with ~ 250 kb of flanking sequence; founder animals (line J1.96) have a single copy of the transgene. | APP: Transgenic | Alzheimer's Disease | No amyloid plaques observed at 2 years. | Unknown. | The Jackson Lab; available through the JAX MMRRC Stock# 034837; Cryopreserved | Lamb et al., 1997 | No | |||
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 K670_M671delinsNL (Swedish), PSEN1 A246E | Double transgenic mice; cross of mice expressing human PSEN1 with the A246E mutation driven by the mouse prion protein promoter with mice expressing chimeric APP (isoform 695) with the Swedish mutation driven by the mouse prion promoter. Chimeric APP was created by replacing the mouse Aβ sequence with the cognate human sequence. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus. | Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task. | Increased irritability. | The Jackson Lab: Stock# 003378; Cryopreserved | Borchelt et al., 1997, Borchelt et al., 1996 | Yes | ||
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 K670_M671delinsNL (Swedish), PSEN1: deltaE9 | Double transgenic mice: 1) Line C3-3: mice express a chimeric mouse/human APP gene (isoform 695) carrying the Swedish mutation and 2) Line S-9: mice express a mutant human PSEN1 gene carrying the deletion of exon 9 (dE9) driven by the mouse prion promoter. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers. | Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months. | At 19 months, small but significant decrease in acetylcholinesterase activity in the hippocampus and choline acetyl transferase (ChAT) in the hippocampus and cortex. | The Jackson Lab; available through the JAX MMRRC Stock# 034833; Cryopreserved | Savonenko et al., 2005 | Yes | ||
APP/PS1, APPswe/PS1deltaE9, line 85, APP(swe) + PSEN1DeltaE9, APPdE9, Borchelt mice | B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax | C57BL/6;C3H | APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | Co-injection of a vector for chimeric mouse/human APP carrying the Swedish mutation and a second for mutant PSEN1 (deltaE9) controlled by independent mouse prion protein promoter elements. The two transgenes co-integrated and co-segragate as a single locus. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity. | Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing). | Kinked tail phenotype that is believed to be due to genetic background. | The Jackson Lab; available through the JAX MMRRC Stock# 034829 (formerly Jackson Lab Stock # 004462); Live | Jankowsky et al., 2001, Jankowsky et al., 2004 | Yes | ||
NSE-APPsw | Origin: C57BL/6 x DBA/2 | APP | APP K670_M671delinsNL (Swedish) | Transgene containing human APP (isoform 695) bearing the Swedish mutation under the control of neuron specific enolase (NSE) promoter. | APP: Transgenic | Alzheimer's Disease | Increased Aβ42 in the cortex and hippocampus of 12 month old mice, but no plaques. Increased tau phosphorylation and TUNEL-stained nuclei relative to control mice. | In water maze tests, 12 month old mice had longer escape latencies than age-matched control mice. | Metallothionein expression was increased in brain astrocytes and was thought to attenuate Aβ-induced neurotoxicity. Increased Cox-2 and caspase-3 compared to age-matched control mice. | Available through Yong K Kim | Hwang et al., 2004 | No | |||
APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line | Inbred C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic) | A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter. | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. | At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. | Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus. | Cryopreserved. Contact Lennart Mucke | Cheng et al., 2004 | Yes | |||
arcAbeta | Origin: B6D2 F1 | APP | APP K670_M671delinsNL (Swedish), APP E693G (Arctic) | Human APP695 transgene containing the Swedish (K670N/M671L) and Arctic mutation (E693G) was generated by site-directed mutagenesis. | APP: Transgenic | Alzheimer's Disease | At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma. | Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze. | Deficits in synaptic plasticity, LTP, and functional connectivity as measured by resting-state fMRI. | Unknown | Knobloch et al., 2007 | Yes | |||
B6;CB-Tg(Thy1-PSEN1*M146V/Thy1-APP*swe)10Arte | Co-injection of transgenes into B6CBF1 oocytes, back-crossed to C57BL/6 | APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146V | Co-integration of two transgenes, mutant APP carrying the K670N/M671L mutation, and mutant PSEN1 carrying the M146V mutation, both under the control of the Thy-1 promoter. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches. | Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months. | Good breeding capabilities and no premature death. | Taconic: Stock #16347 | Willuweit et al., 2009 | Yes | |||
APOE2-FAD, APOE2 Targeted Replacement x 5xFAD | C57BL/6 | APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE2 Targeted Replacement mice were crossed with the 5xFAD line. | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. | In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice. | 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE2 Targeted Replacement mice are available through Taconic, Stock# 1547-F or 1547-M. | Youmans et al., 2012 | Yes | ||||
APOE3-FAD, APOE3 Targeted Replacement x 5xFAD | C57BL/6 | APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE3 Targeted Replacement mice were crossed with the 5xFAD line. | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. | In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice. | 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE3 Targeted Replacement mice are available through Taconic, Stock# 1548-F or 1548-M. | Youmans et al., 2012 | Yes | ||||
APOE4-FAD, APOE4 Targeted Replacement x 5xFAD | C57BL/6 | APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE4 Targeted Replacement mice were crossed with the 5xFAD line. | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. | Age-dependent learning and memory deficits in the Y maze and Morris water maze. | 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE4 Targeted Replacement mice are available through Taconic, Stock# 1549-F or 1549-M. | Youmans et al., 2012 | Yes | ||||
PDGF-APPSw,Ind, PDGF-hAPP695,751,770V171F, KM670/671NL, hAPPJ20, hAPP, Mucke mice | B6.Cg-Zbtb20Tg(PDGFB-APPSwInd)20Lms/2Mmjax | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. | APP: Transgenic | Alzheimer's Disease | Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity. | Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated. | On the C57BL/6J background hippocampal hyperexcitability was observed and cortical and hippocampal spontaneous nonconvulsive seizures. | The Jackson Lab; available through the JAX MMRRC Stock# 034836-JAX; Live | Mucke et al., 2000 | Yes | ||
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 K670_M671delinsNL (Swedish), APP V717I (London) | The transgene over-expresses the mutant human amyloid protein precursor (751 isoform), which bears both the Swedish (K670N/M671L) and the London (V717I) mutations, under the control of the murine Thy1 promoter. | APP: Transgenic | Alzheimer's Disease | Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region. | Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration. | Available through Eliezer Masliah. The CRO PsychoGenics offers research services with this line. | Rockenstein et al., 2001 | Yes | |||
APP(Swedish,Indiana), line J9, hAPPJ9, hAPPlow | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. | APP: Transgenic | Alzheimer's Disease | Amyloid plaques at 8-10 months, but not at 2-4 months when deficits in synaptic transmission are observed. Approximately 20% of mice had plaques at 5-7 months, 50% at 8-10 months, and 100% by 21-25 months. | Unknown. | Deficits in synaptic transmission at 2-4 months, prior to amyloid deposition. | Available through Lennart Mucke | Hsia et al., 1999 | No | |||
hAPP/hTau/hPS1, PLB1(Triple) | C57BL6 | APP, MAPT, PSEN1 | APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W | Targeted insertion of human APP and tau sequences at the HPRT site on the X chromosome, driven by mouse CaMKII-α. Human APP (isoform 770) with the Swedish and London mutations. Human tau (isoform 2N/4R, 441 amino acids) with P301L and R406W. APP/tau-expressing animals (PLB1-double) were crossed with hPS1 (A246E) transgenic mice (Borchelt et al., 1997) to generate the triple transgenic. | APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene | Alzheimer's Disease | Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT. | Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity. | Litter size and overall health were normal. Mice spent more time awake at six months and had fragmented sleep. Quantitative EEG showed heightened delta power during wakefulness and REM sleep. | Available through Bettina Platt | Platt et al., 2011 | Yes | |||
B6.PS2APP, TG B6.PS2APP mice (line B6.152H) | Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz | C57BL/6 | APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | Coinjection of two transgenes into C57/Bl/6 zygotes: Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter and human APP751 with the Swedish mutation driven by the Thy1.2 promoter. | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months. | Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months. | Decreased survival of newborn neurons in the dentate gyrus at about 4 months. Reduced endoplasmic reticulum Ca2+ and calcium dysregulation. A strong increase in LTP and post-tetanic potentiation (PTP) in hippocampal slices of 10 month old animals compared to wild-type mice. Decreased perfusion in the occipital cortex at all ages tested (10-17 months). | Available through Laurence Ozmen | Ozmen et al., 2009 | Yes | ||
PS2(N141I) x APPswe , hPS2(N141I) x hAPPswe | Tg(Thy1-APPSwe)71Jgr x Tg(Prnp-PSEN2*N141I)30Jgr | C57BL/6, DLB/2, crossed to C57BL/6 | APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | Double transgenics created by crossing APPSwe mice (transgene containing the 751 isoform of human APP with the Swedish mutation driven by the Thy1.2 promoter) with PS2(N141I) mice (tansgene containing human PSEN2 with the N141I mutation driven by the mouse prion protein promoter). | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition. | Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze. | More insoluble Aβ40 and Aβ42 than age-matched APPSwe mice at 16-18 months. Loss of metabotropic glutamate receptors (mGlu2) in certain brain regions of aged mice as demonstrated by autoradiography. | Available through Laurence Ozmen | Richards et al., 2003 | Yes | ||
PS1 + APP, PSAPP, APP/PS1, APP/PS1 double transgenic | B6/D2/Swe/SJL mixed background | APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C) | These double transgenic mice were generated by crossing mice overexpressing human APP with the Swedish mutation driven by the hamster prion protein gene promoter (the Tg2576 model) with mice overexpressing human PSEN1 with the M146L mutation driven by the PDGF-β promoter (PSEN1(M146L), line 5.1). The two transgenes segregate independently. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter, cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation. | Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels. | Selective increase in brain Aβ42(43) in the double transgenics (41% increase at 6 weeks) compared to Tg2576 single transgenic, which had unchanged Aβ40 and Aβ42(43) at this age. | Tg2576: Taconic (Stock #001349) and Charles River; PS1(M146L): University of South Florida Technology Transfer Office. The CRO PsychoGenics offers research services with Tg2576 and the double transgenic line. | Holcomb et al., 1998 | Yes | |||
APPNLI | 129S6FVB F1 | APP | APP K670_M671delinsNL (Swedish), APP V717I (London) | These are bigenic mice with the CAMKII-α promoter driving expression of tetracycline transactivator (tTa) in excitatory neurons in the forebrain, and a responder transgene consisting of mutant human APP (isoform 695) carrying the Swedish and London mutations. The expression of the transgene is constitutive until suppressed by doxycycline. | APP: Transgenic | Alzheimer's Disease | Age-associated pathology in the cerebral cortex and hippocampus starting at 8 and 10½-12½ months of age, respectively. Gliosis and hyperphosphorylated tau in the vicinity of dense-core plaques. Fibrillar oligomeric species, e.g., Aβ dimers. | No transgene-related deficits seen in Morris water maze (4, 12, 21, 24, months of age) or fixed consecutive-number (23 months of age) tests. | Reduced body weight at 24-27 months relative to non-Tg littermates and those expressing only tTA. | Available through Karen Ashe | Liu et al., 2015 | Yes | |||
thy1-APPswe | Transgene injected into C57BL/6 x C3H oocytes, some backcrossing to C57BL/6 | APP | APP K670_M671delinsNL (Swedish) | Transgene expresses human APP (isoform 695) harboring the Swedish mutation, driven by the murine Thy-1 promoter. | APP: Transgenic | Alzheimer's Disease | Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes. | Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning. | No differences in body temperature, locomotor activity, or Rotarod performance, relative to non-Tg controls. | Unknown | Richardson et al., 2003 | Yes | |||
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 K670_M671delinsNL (Swedish), PSEN1 M146V | This is a double transgenic model generated by crossing TAS10 mice (an APP transgenic line expressing human APP695 with the Swedish mutation) with TPM mice (a PSEN1 transgenic expressing human PSEN1 with the M146V mutation). Both transgenes are driven by the murine Thy-1 promoter. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Aβ deposits beginning at 3 months of age, with fibrillar plaques by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid. Plaques surrounded by dystrophic neurites and reactive glia. No tangles or neuronal loss. Female mice have more rapid and severe amyloid pathology. | Age-dependent impairment in object recognition memory starting around 6 months of age. | Unknown | Howlett et al., 2004 | Yes | ||||
Triple transgenic, 3Tg | B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L) | C57BL/6, DBA/2; backcrossed to C57BL/6 | APP, MAPT, PSEN2 | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I | PS2APP mice (line B6.152H) x tau mice (line B6.TauP301L). PS2APP were generated by co-injecting two transgenic constructs: human PSEN2 (N141I mutation) and human APP (Swedish mutation) driven by the mouse prion promoter and the mouse Thy1 promoter respectively. The transgenic TauP301L mouse (line pR5) expresses the human tau40 isoform driven by the Thy1.2 promoter. | APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss. | Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology. | Cortex-specific deficiencies in oxidative phosphorylation. Loss of mitochondrial membrane potential. Reduced cortical ATP. Increased superoxide anions and ROS compared to wild-type. No differences in APP expression, APP cleavage or Aβ accumulation compared to PS2APP. Levels of ptau422 increased in an age-dependent manner, but levels of ptau231 did not. | Available through Laurence Ozmen | Grueninger et al., 2010 | Yes | ||
line 102 | B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax | C57BL/6 x C3HeJ; backcrossed to C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. | APP: Transgenic | Alzheimer's Disease | APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest doxycycline sensitivity relative to lines 107 and 885. | Hyperactivity. | The Jackson Lab; available through the JAX MMRRC Stock# 034845; Cryopreserved | Jankowsky et al., 2005 | No | |||
line 107 | B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax | C57BL/6 x C3HeJ; backcrossed to C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. | APP: Transgenic | Alzheimer's Disease | APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Intermediate expression of transgene and doxycycline sensitivity relative to lines 102 and 885. | Hyperactivity. | The Jackson Lab; available through the JAX MMRRC Stock# 034846; Cryopreserved | Jankowsky et al., 2005 | No | |||
line 885 | B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax | C57BL/6 x C3HeJ; backcrossed to C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. | APP: Transgenic | Alzheimer's Disease | APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest transgene expression and highest doxycycline requirement relative to lines 102 and 107. | Hyperactivity. | The Jackson Lab; available through the JAX MMRRC Stock# 034834; Cryopreserved | Jankowsky et al., 2005 | No | |||
Hsiao mice, App-Swe, App-sw, APP(sw), APPSwe | B6;SJL-Tg(APPSWE)2576Kha | B6;SJL Mixed Background | APP | APP K670_M671delinsNL (Swedish) | The human APP gene (isoform 695) containing the double mutation K670N, M671L (Swedish mutation) under the control of the hamster prion protein. | APP: Transgenic | Alzheimer's Disease | Numerous parenchymal Aβ plaques by 11-13 months with some vascular amyloid. Oxidative lipid damage, astrogliosis and microgliosis. No tangles or neuronal loss. | Impaired spatial learning, working memory, and contextual fear conditioning reported at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months. | Between 7 -12 weeks males become aggressive and begin to fight. Premature mortality: mortality of >20% anticipated, particularly in males. | Taconic: Stock #1349 and Charles River. The CROs PsychoGenics and QPS Austria offer 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 K670_M671delinsNL (Swedish), MAPT P301L | Generated by crossing Tg2576 mice, which have the transgene for human APP (isoform 695) carrying the Swedish mutation with mice expressing human MAPT (4 repeat) with the P301L mutation. | APP; MAPT: Transgenic | Alzheimer's Disease | Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis. | Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming. | Progressive hindlimb weakness. Hunched posture. Eye irritations. Some mice have the Pde6brd1 retinal degeneration mutation which can cause light sensitivity and/or blindness and may affect behavioral testing. | Taconic: Stock# 2469 | Lewis et al., 2001 | Yes | ||
Tg-Swe | C57BL/6J | APP | APP K670_M671delinsNL (Swedish) | Transgene with human APP (isoform 695) bearing the Swedish mutation under the murine Thy1 promoter. | APP: Transgenic | Alzheimer's Disease | Extracellular amyloid deposition begins at ~12 months. Intraneuronal Aβ aggregates at ~6 months. Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1.0% (at 12 months) and 2.8% (at 18 months). | Unknown. | Available through Lars Nilsson | Philipson et al., 2009, Lord et al., 2006 | Yes | ||||
R1 line of ES cells | APP | APP K670_M671delinsNL (Swedish) | Modification of mouse APP sequence to introduce the Swedish mutation and "humanize" the murine Aβ sequence by altering three amino acids. | APP: Knock-In | Alzheimer's Disease | Accumulation of human Aβ. | Unknown. | Unknown | Reaume et al., 1996 | No | |||||
tg ArcSwe, APP-ArcSwe | C57BL/6J | APP | APP K670_M671delinsNL (Swedish), APP E693G (Arctic) | Transgene with human APP (isoform 695) containing both the Arctic (E693G) and Swedish (KM670/671NL) mutations under the murine Thy1 promoter. | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus. | Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months. | Tg-ArcSwe have reduced body weight compared with nontransgenic littermates. | Available through Lars Nilsson | Lord et al., 2006 | Yes | |||
APP(swe/ind) CRND8 | Hybrid C3H/He-C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Transgene contains human APP695 with the Swedish mutation (KM670/671/NL) and Indiana mutation (V717F) under the control of the hamster prion (PrP) gene promoter. The expression cassette includes about 90 nucleotides of the APP 5'-untranslated region adjacent to the start codon and 269 nucleotides of the 3′-untranslated region. | APP: Transgenic | Alzheimer's Disease | Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months . | Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests. | Cholinergic dysfunction: decrease in the number of cholinergic neurons in the nucleus basalis magnocellularis by 7 months as measured by ChAT immunoreactivity. Enhanced auditory startle response and modest reduction in prepulse inhibition. | Available through the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto | Chishti et al., 2001 | Yes | |||
mAPP/DN-RAGE, APP/DN-RAGE | C57BL/6 | APP, RAGE (AGER) | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mice expressing a form of transgenic RAGE comprising a truncated form of the receptor with intact extracellular and membrane-spanning portions, but a deleted cytosolic tail driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661--now extinct). | APP: Transgenic; RAGE (AGER): Transgenic | Alzheimer's Disease | Diminished neuropathology compared with mice expressing mutant APP alone at both 3–4 and 14–18 months of age. | Preservation of spatial learning and memory compared with Tg-mAPP/RAGE animals. | No abnormalities with respect to reproductive fitness, development, basic neurological functioning, or longevity. | Available through Shirley ShiDu Yan | Arancio et al., 2004 | No | |||
APP/RAGE | C57BL/6 | APP, RAGE (AGER) | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mice expressing human wild-type RAGE driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661-now extinct) | APP: Transgenic; RAGE (AGER): Transgenic | Alzheimer's Disease | Increased activation of microglia and astrocytes compared to mice expressing mutant APP alone. | Abnormalities in spatial learning and memory at 3-4 months of age, whereas deficits occur later in mice expressing mutant APP alone and are less severe. | Available through Shirley ShiDu Yan | Arancio et al., 2004 | No | ||||
APP-Swedish,Dutch,Iowa, APPSwDI | C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) | Transgenic mice with 2.1 kb of the human APP gene (isoform 770) with the Swedish (K670N/M671L), Dutch (E693Q) and Iowa (D694N) mutations under the control of the mouse Thy1 promoter. | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type | Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months. | Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination. | The Jackson Lab; available through the JAX MMRRC Stock# 034843; Live | Davis et al., 2004 | Yes |
39 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
-
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).
-
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).
-
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.
-
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).
-
Cognitive Impairment at 17
Cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Aβ in the hippocampus and amygdala, but plaques and tangles are not yet apparent (Billings et al., 2005).
Absent
No Data
-
Neuronal Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Psen1, APP, MAPT | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V | Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic | Alzheimer's Disease | Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. |
Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task. |
5xFAD (B6SJL)
Observed
-
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.
-
Neuronal Loss at 24
Neuron loss in cortical layer V and subiculum.
-
Gliosis at 8
Gliosis begins at 2 months.
-
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
-
Changes in LTP/LTD at 24
Basal synaptic transmission and LTP in hippocampal area CA1 begin to deteriorate between 4 and 6 months
-
Cognitive Impairment at 18
Impaired spatial working memory in the Y-maze test and impaired remote memory stabilization in a contextual-fear-conditioning test by 4 to 5 months of age.
Absent
-
Tangles at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles. |
Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype. |
A7 APP transgenic
Observed
-
Plaques at 39
These mice develop progressive amyloid deposition in the cerebral cortex by 9-12 months. By 21 months of age amyloid pathology is extensive.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP T714I (Austrian) | APP: Transgenic | Alzheimer's Disease | Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months. |
Unknown. |
APP23
Observed
-
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).
-
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).
-
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).
-
Cognitive Impairment at 13
Spatial memory defects in Morris Water maze at 3 months and progresses with age (Van dam et al., 2003; Kelly et al., 2003).
Absent
-
Tangles at
Dystrophic neurites containing hyperphopshorylated tau surounds Aβ plaques, but no neurofibrillary tangles are observed (Sturchler-Pierrat et al., 1997).
-
Synaptic Loss at
Neocortical synapses were examined in mice as old as 24 months of age; no evidence of alterations in the number of synapses or levels of synaptophysin were observed (Boncristiano et al., 2005).
-
Changes in LTP/LTD at
LTP in the hippocampus and prefrontal cortex is normal at all ages studied: 3, 6, 9, 12, 18 and 24 months (Roder at al., 2003).
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish) | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages. |
Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages. |
APP751SL/PS1 KI
Observed
-
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).
-
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).
-
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).
-
Synaptic Loss at 24
At 6 months, levels of pre- and post-synaptic markers are reduced (Breyhan et al., 2009).
-
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).
-
Cognitive Impairment at 27
Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates (Wirths et al., 2008).
Absent
-
Tangles at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P | APP: Transgenic; PSEN1: Knock-In | Alzheimer's Disease | Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons. |
Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates. |
APP751-SL x THMT
Observed
-
Plaques at 13
Plaques start at 3 months in the frontal cortex and become more widespread with age.
-
Gliosis at 26
Microglial activation. Numerous glial cells around amyloid plaques at 6 months.
-
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 K670_M671delinsNL (Swedish), APP V717I (London), MAPT V337M, 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. |
APP NL-F Knock-in
Observed
-
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.
-
Gliosis at 26
Microglia and activated astrocytes accumulate with age, starting around 6 months of age, concurrent with plaque formation.
-
Synaptic Loss at 39
Reduced synaptophysin and PSD95 immunoreactivities associated with Aβ plaques at 9-12 months.
-
Cognitive Impairment at 78
Memory impairment in homozygous mice at 18 months as measured by the Y maze test. APPNL/NL mice (with Swedish mutation only) were unimpaired at this age. No significant deficit was seen in the Morris water maze at 18 months.
Absent
-
Tangles at
Absent; although elevated levels of phosphorylated tau are observed in dystrophic neurites around plaques.
-
Neuronal Loss at
Absent.
No Data
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP I716F (Iberian) | APP: Knock-In | Alzheimer's Disease | Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. |
Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. |
APP NL-G-F Knock-in
Observed
-
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.
-
Gliosis at 9
Microglia and activated astrocytes accumulate with age starting around 2 months, especially around plaques in a manner concurrent with plaque formation.
-
Synaptic Loss at 17
Reduction of synaptophysin and PSD95 immunoreactivities associated with Aβ plaques in both cortical and hippocampal areas.
-
Cognitive Impairment at 26
Memory impairment in homozygous mice by 6 months of age as measured by the Y maze.
Absent
-
Tangles at
Absent; although phosphorylated tau is elevated in dystrophic neurites around plaques.
-
Neuronal Loss at
Absent.
No Data
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) | APP: Knock-In | Alzheimer's Disease | Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. |
Memory impairment by 6 months as measured by the Y maze. |
APPPS1
Observed
-
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).
-
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).
-
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).
-
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).
-
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).
-
Cognitive Impairment at 30
Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006).
Absent
-
Tangles at
Phosphorylated tau-positive neuritic processes around plaques have been observed, but no mature tangles (Radde et al., 2006).
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 L166P | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.
|
Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months. |
APP/PS1/rTg21221
Observed
-
Plaques at 35
Cortical plaques observed between 8-10 months. Plaques larger than in control mice not expressing human tau.
-
Neuronal Loss at 36
Neuronal loss observed adjacent to plaques relative to more distal areas.
-
Gliosis at 37
Increased astrocytosis adjacent to plaques relative to more distal areas.
-
Synaptic Loss at 40
Decreased synapse density adjacent to plaques relative to more distal areas.
Absent
-
Tangles at
No tangles. Aggregates of misfolded and phosphorylated tau observed between 8-10 months.
No Data
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1, MAPT | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic | Alzheimer's Disease | Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed. |
No data. |
APPsw/0; Pdgfrβ+/-
Observed
-
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.
-
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.
-
Cognitive Impairment at 41
At nine months, APPsw/0;Pdgfrβ+/- mice perform poorly on several hippocampal-dependent behavioral tests including burrowing, nest construction, and novel object recognition, compared with age-matched APPsw/0;Pdgfrβ+/+ littermates.
Absent
No Data
-
Tangles at
Although mature neurofibrillary tangles were not observed by 9 months (the oldest age assessed), the mice develop significant tau pathology, including tau hyperphosphorylation in cortical and hippocampal neurons. Pre-tangle pathology is observed, including neuronal caspase-cleaved tau, and conformational changes as indicated by the conformation-specific antibody MC1.
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PDGFRB | APP K670_M671delinsNL (Swedish) | APP: Transgenic; PDGFRB: Knock-Out | Alzheimer's Disease | Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus. |
Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition. |
APPSwDI x NOS2 Knock-out
Observed
-
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).
-
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).
-
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).
-
Cognitive Impairment at 53
Impairments in spatial memory by 52-56 weeks as measured by the radial arm maze and the Barnes maze. Bigenic mice more impaired than APPSwDI (Wilcock et al., 2008).
Absent
No Data
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, NOS2 | APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) | APP: Transgenic; NOS2: Knock-Out | Alzheimer's Disease | Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone. |
Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks. |
APP(Swedish) (R1.40)
Observed
-
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).
-
Gliosis at 61
Reactive astrocytes and microglia in 14-16 month old animals (Kulnane et al., 2001).
Absent
-
Tangles at
No mature tangles, but some changes in phosphorylated tau.
-
Changes in LTP/LTD at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
-
Cognitive Impairment at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish) | APP: Transgenic | Alzheimer's Disease | By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months. |
Unknown. |
APPSwe (line C3-3)
Observed
-
Plaques at 104
Some plaque formation at advanced age (24-26 months) (Savonenko et al., 2003).
Absent
-
Cognitive Impairment at
Normal reference and working memory up to 12-14 months on congenic background (Savonenko et al., 2003).
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish) | APP: Transgenic | Alzheimer's Disease | Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age. |
Congenic animals showed normal reference and working memory up to 12-14 months. |
APPSwe/PSEN1(A246E)
Observed
-
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).
-
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).
-
Cognitive Impairment at 48
Age-associated cognitive impairment, as measured by the Morris water maze, was observed in 11 to 12-month-old males. Both acquisition and retention were impaired. No impairment at 3-4 months of age. At both time points mice performed normally on a position discrimination task in the T-maze (Puoliväli et al., 2002).
Absent
-
Tangles at
Not observed.
-
Neuronal Loss at
There was no difference in neuronal numbers in the cingulate cortex compared with wild-type mice (Xiang et al., 2002).
No Data
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 A246E | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus. |
Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task. |
APPSwe/PSEN1dE9 (C3-3 x S-9)
Observed
-
Plaques at 26
Plaques are present in the hippocampus and cortex by 6 months of age.
-
Cognitive Impairment at 78
Age-related cognitive deficits. Episodic memory appears to be more sensitive than reference memory. No differences at 6 months of age, but detectable at 18 months (Savonenko et al., 2005).
Absent
-
Tangles at
Not observed.
No Data
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers. |
Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months. |
APPswe/PSEN1dE9 (line 85)
Observed
-
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).
-
Neuronal Loss at 35
Neuronal loss observed adjacent to plaques relative to more distal areas.
-
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).
-
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).
-
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).
-
Cognitive Impairment at 52
Impairment in the Morris water maze at 12 months, specifically during acquisition of the hidden platform sub-task and the probe trial, but not in the visible platform test (Lalonde et al., 2005). At 13 months the mice commit more errors in the Morris water maze, but not at 7 months (Volianskis et al., 2008).
Absent
-
Tangles at
Not observed.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity. |
Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing). |
Arc48 (APPSw/Ind/Arc)
Observed
-
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).
-
Gliosis at 13
Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).
-
Cognitive Impairment at 13
At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but were impaired in the ability to use extramaze cues to navigate to the hidden platform (Cheng et al., 2007).
Absent
-
Tangles at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic) | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. |
At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. |
ArcAβ
Observed
-
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).
-
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).
-
Cognitive Impairment at 26
Cognitive impairment measured from the age of 6 months in the Morris water maze and Y-maze, as well as in active avoidance behavior (Knobloch et al., 2007).
Absent
-
Tangles at
Absent.
No Data
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP E693G (Arctic) | APP: Transgenic | Alzheimer's Disease | At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma. | Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze. |
ARTE10
Observed
-
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.
-
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.
-
Synaptic Loss at 13
Decreased expression of synaptophysin mRNA in the brain by 3-4 months of age in both hemizygous and homozygous animals.
-
Cognitive Impairment at 52
Select, paradigm-dependent, deficits in learning and memory, especially episodic memory, by 12 months in homozygous and hemizygous mice.
Absent
-
Tangles at
No tangles or neuropil threads, but some hyperphosphorylated tau by eight months in dystrophic neurites.
-
Neuronal Loss at
Outright neuronal loss has not been documented, but substantial degeneration of dendritic arbors occurs by 10-14 months of age in hippocampal neurons.
No Data
-
Changes in LTP/LTD at
Unknown; however, hippocampal neurons exhibit substantial changes in electrophysiological properties by 10-14 months of age, including hyperexcitability in the form of increased firing of action potentials and a more efficient transition from solitary firing to bursting.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146V | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches. |
Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months. |
E2FAD
Observed
-
Plaques at 17
Plaques develop in the subiculum and deep cortical layers by 4 months.
-
Gliosis at 26
Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
-
Synaptic Loss at 17
Protein levels of NMDA receptor subunits decreased from 2 to 6 months.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
E2FAD mice had performance in learning and memory tasks comparable to E3FAD animals and better than E4FAD mice.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. |
In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice. |
E3FAD
Observed
-
Plaques at 17
Plaques develop in the subiculum and deep cortical layers by 4 months.
-
Gliosis at 26
Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
-
Synaptic Loss at 17
Protein levels of NMDA receptor subunits decreased from 2 to 6 months.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
E3FAD mice had performance in learning and memory tasks comparable to E4FAD and E2FAD animals.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. |
In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice. |
E4FAD
Observed
-
Plaques at 17
Plaques develop in the subiculum and deep cortical layers by 4 months.
-
Gliosis at 26
Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
-
Synaptic Loss at 17
Decreased protein levels of PSD95 and NMDA receptor subunits by 4 months.
-
Cognitive Impairment at 8
Modest learning deficits in the Morris water maze by 2 months. Progressive decrease in performance on learning and memory tasks.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. |
Age-dependent learning and memory deficits in the Y maze and Morris water maze. |
J20 (PDGF-APPSw,Ind)
Observed
-
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).
-
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).
-
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).
-
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).
-
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).
-
Cognitive Impairment at 16
Deficits in spatial memory and learning appear as the mice age. By 4 months, J20 mice demonstrate spatial reference memory deficits as measured by the radial arm maze (Wright et al., 2013) and Morris water maze (Cheng et al., 2007).
Absent
-
Tangles at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | APP: Transgenic | Alzheimer's Disease | Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity. |
Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated. |
mThy1-hAPP751 (TASD41)
Observed
-
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).
-
Gliosis at 27
Inflammation related to activated microglia (increased CD11) and reactive astrocytes (increased GFAP) is significant by 6 months and increases with age.
-
Synaptic Loss at 52
Dystrophic neurites and synaptic loss starting at 12 months.
-
Cognitive Impairment at 26
Cognitive impairment observed by 6 months by Morris Water Maze (Rockenstein et al., 2005).
Absent
-
Tangles at
Absent.
-
Neuronal Loss at
Absent.
No Data
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP V717I (London) | APP: Transgenic | Alzheimer's Disease | Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region. |
Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration. |
PLB1-triple (hAPP/hTau/hPS1)
Observed
-
Gliosis at 52
Increased inflammation (GFAP labelling) detected at 12 months in cortex and hippocampus (Platt, unpublished observation).
-
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.
-
Cognitive Impairment at 22
Social recognition memory was impaired by five months and further impaired by 12 months. Similarly, object recognition memory was impaired by eight months. Spatial learning impairments were seen later; at 12 months deficits in spatial acquisition learning were seen in the open field water maze that were not apparent at 5 months.
Absent
-
Plaques at
Sparse plaques out to 21 months of age. Only marginally increased compared with wild-types and overall very low compared to over-expression models. However, Aβ accumulated intracellularly and also formed oligomers.
-
Tangles at
No overt tangle pathology; however, hyyperphosphorylated tau accumulated in the hippocampus and cortex from six months of age.
-
Neuronal Loss at
Absent.
No Data
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, MAPT, PSEN1 | APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W | APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene | Alzheimer's Disease | Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT. |
Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity. |
PS2APP
Observed
-
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).
-
Gliosis at 26
Gliosis at 6 months (personal communication, Laurence Ozmen).
-
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).
-
Cognitive Impairment at 35
Cognitive impairment is detected by the Morris water maze (probe trial 2) at 8 and 12 months of age, not at 3 months (personal communication Laurence Ozmen).
Absent
-
Tangles at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months. |
Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months. |
PS2APP (PS2(N141I) x APPswe)
Observed
-
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).
-
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.
-
Cognitive Impairment at 35
Age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze (Richards et al., 2003).
Absent
-
Tangles at
Absent.
-
Changes in LTP/LTD at
No difference in LTP in the dentate gyrus at 3 and 10 months compared to wild-type mice (Richards et al., 2003).
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition. |
Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze. |
PS/APP
Observed
-
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).
-
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).
-
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).
-
Cognitive Impairment at 12
Double and single transgenic mice had reduced spontaneous alternation performance in a “Y” maze, a test of spatial memory, at 12-14 weeks, before substantial Aβ deposition (Holcomb et al., 1998). Progressive age-related cognitive impairment is seen later in select tasks (e.g. water maze acquisition and radial arm water maze working memory)(Arendash et al., 2001).
Absent
-
Tangles at
Neurofibrillary tangles are not associated with this model, but hyperphosphorylated tau is detected, starting at 24 weeks, appearing as punctate deposits near amyloid deposits in the cortex and hippocampus (Kurt et al., 2003).
No Data
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C) | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter, cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation. |
Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels. |
rTg9191
Observed
-
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.
-
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).
-
Gliosis at 104
rTg9191 mice develop reactive gliosis (astrocytosis and microgliosis) in the vicinity of dense-core plaques by 24 months of age.
Absent
-
Tangles at
Tangles are not observed, but hyperphosphorylated tau develops with age.
-
Cognitive Impairment at
No transgene-related deficits seen in Morris water maze (4, 12, 21, 24 months of age) or fixed consecutive number test (23 months of age).
No Data
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP V717I (London) | APP: Transgenic | Alzheimer's Disease | Age-associated pathology in the cerebral cortex and hippocampus starting at 8 and 10½-12½ months of age, respectively. Gliosis and hyperphosphorylated tau in the vicinity of dense-core plaques. Fibrillar oligomeric species, e.g., Aβ dimers. |
No transgene-related deficits seen in Morris water maze (4, 12, 21, 24, months of age) or fixed consecutive-number (23 months of age) tests. |
TAS10 (thy1-APPswe)
Observed
-
Plaques at 52
Fibrillar amyloid plaques develop by 12 months in the cortex and hippocampus.
-
Gliosis at 26
Astrogliosis and microgliosis underway by 6 months of age in the dentate gyrus.
-
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.
-
Cognitive Impairment at 26
Deficits in spatial learning present by 6 months of age as measured by the Morris water maze. No difference from non-Tg at 2 months of age. Deficits in Y maze at 12 months. No deficit in fear conditioning up to 24 months of age.
Absent
-
Tangles at
Absent.
-
Neuronal Loss at
Qualitative difference in neuronal numbers at 24 months in specific regions of the hippocampus, but no significant neuronal loss.
-
Changes in LTP/LTD at
At 12 to 14 months of age, deficits in basal synaptic transmission have been observed in the CA1 region, but short- and long-term synaptic plasticity are relatively normal (Brown et al., 2005).
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish) | APP: Transgenic | Alzheimer's Disease | Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes. |
Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning. |
TASTPM (TAS10 x TPM)
Observed
-
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.
-
Gliosis at 28
Greater numbers of reactive astrocytes and microglia by 6 months of age in the hippocampus and cortex, predominantly near amyloid plaques.
-
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 K670_M671delinsNL (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. |
TauPS2APP
Observed
-
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).
-
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).
-
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 K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I | 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. |
Tg2576
Observed
-
Plaques at 48
Numerous parenchymal Aβ plaques by 11-13 months.
-
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).
-
Synaptic Loss at 20
Dendritic spine loss by 4.5 months In the CA1 region of the hippocampus (Lanz et al., 2003).
-
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).
-
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 K670_M671delinsNL (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. |
Tg2576/Tau(P301L) (APPSwe-Tau)
Observed
-
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.
-
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).
-
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 K670_M671delinsNL (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. |
tg-APPSwe
Observed
-
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).
-
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 K670_M671delinsNL (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. |
Tg-ArcSwe
Observed
-
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).
-
Gliosis at 26
Microgliosis and astrogliosis most prominent in the hippocampus, but also locally around deposits in the cerebral cortex and thalamus.
-
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 K670_M671delinsNL (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. |
TgCRND8
Observed
-
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).
-
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).
-
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).
-
Synaptic Loss at 26
Reduced synaptophysin immunoreactivity in the vicinity of plaques at 6 months (Adalbert et al., 2009).
-
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).
-
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 K670_M671delinsNL (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. |
Tg-SwDI (APP-Swedish,Dutch,Iowa)
Observed
-
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).
-
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).
-
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 K670_M671delinsNL (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. |