Research Models

Selected Results

12 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathology Behavior/Cognition Other Phenotype Availability Primary Paper Visualization
Mouse Models (12)
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
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
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
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
Knock-in of APP(V642I) Origin:C57BL/6 x CBA; chimeric mice breed to CD-1 mice APP APP V717I (London) Targeted knock-in of the V642I mutation into exon 17 of the mouse APP gene using homologous recombination and the Cre-loxP system. APP: Transgenic Alzheimer's Disease Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy. At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels. Unknown Kawasumi et al., 2004 Yes
APPlon, APP-london, APPLd, APP-ld, APP(V717I), APP[V717I], APP.V717I, APP(London) (line 2), APP/LD/2 Tg(Thy1-APPLon)2Vln/0 Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N APP APP V717I (London) Transgene containing human APP (isoform 695) with the London mutation driven by the Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology. From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression. Increased mortality (72% by day 180). Increased incidence of seizures. Available through the KU Leuven Research and Development Office; the CRO reMYND offers research services with this line. Moechars et al., 1999 Yes
APPxPS1, APP(V717I)x PS1(A246E), APP[V717I]x PS1[A246E], APP.V717I x PS1.A246E Tg(Thy1-APPLon)2Vln/0; Tg(Thy1-PSEN1*A246E)2Vln/0 Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N APP, PSEN1 APP V717I (London), PSEN1 A246E The transgene overexpresses the mutant human amyloid protein precursor APP (isoform 695), which bears the London (V717I) mutation, and human presenilin-1 with the A246E mutation, both under the control of the neuron-specific murine Thy1 promoter. APP: Multi-transgene; PSEN1: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology. From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression. The CRO reMYND offers research services with this line. Dewachter et al., 2000 Yes
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
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
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

9 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+.

5xFAD (B6SJL)

Observed
  1. X
    Plaques at 8

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

  2. X
    Neuronal Loss at 24

    Neuron loss in cortical layer V and subiculum.

  3. X
    Gliosis at 8

    Gliosis begins at 2 months.

  4. X
    Synaptic Loss at 16

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

  5. X
    Changes in LTP/LTD at 24

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

  6. X
    Cognitive Impairment at 18

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

Absent
  • Tangles at

    Absent.

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

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

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

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APP751SL/PS1 KI

Observed
  1. X
    Plaques at 11

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

  2. X
    Neuronal Loss at 23

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

  3. X
    Gliosis at 11

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

  4. X
    Synaptic Loss at 24

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

  5. X
    Changes in LTP/LTD at 28

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

  6. X
    Cognitive Impairment at 27

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

Absent
  • Tangles at

    Absent.

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

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

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

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APP751-SL x THMT

Observed
  1. X
    Plaques at 13

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

  2. X
    Gliosis at 26

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

  3. X
    Cognitive Impairment at 13

    Cognitive impairment at 3 months demonstrated by Morris Water Maze.

Absent
No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, APP APP 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.

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APP(V642I)KI

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

    Absent.

  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

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

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

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

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APP(V717I)

Observed
  1. X
    Plaques at 43

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

  2. X
    Gliosis at 43

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

  3. X
    Changes in LTP/LTD at 26

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

  4. X
    Cognitive Impairment at 26

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

Absent
  • Tangles at

    Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

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

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

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

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APP(V717I) x PS1(A246E)

Observed
  1. X
    Plaques at 17

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

  2. X
    Gliosis at 20

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

  3. X
    Changes in LTP/LTD at 26

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

  4. X
    Cognitive Impairment at 22

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

Absent
  • Tangles at

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

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

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

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

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mThy1-hAPP751 (TASD41)

Observed
  1. X
    Plaques at 13

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

  2. X
    Gliosis at 27

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

  3. X
    Synaptic Loss at 52

    Dystrophic neurites and synaptic loss starting at 12 months.

  4. X
    Cognitive Impairment at 26

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

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

No Data
  • Changes in LTP/LTD at

    Unknown.

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

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

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

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PLB1-triple (hAPP/hTau/hPS1)

Observed
  1. X
    Gliosis at 52

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

  2. X
    Changes in LTP/LTD at 26

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

  3. X
    Cognitive Impairment at 22

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

Absent
  • Plaques at

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

  • Tangles at

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

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

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

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

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

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rTg9191

Observed
  1. X
    Plaques at 35

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

  2. X
    Neuronal Loss at 9

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

  3. X
    Gliosis at 104

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

Absent
  • Tangles at

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

  • Cognitive Impairment at

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

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

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

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

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

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