Research Models

Selected Results

8 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 (8)
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
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
BAC-TREM2 X 5xFAD TREM2-BAC: FVB/NJ; 5xFAD: C57BL/6 X SJL TREM2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V TREM2-BAC mice were crossed with 5xFAD mice. TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques with plaque-associated microgliosis. Reduced plaque burden, altered microglial and plaque morphology, and less severe plaque-associated neuritic dystrophy, compared with 5xFAD. 5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired. TREM2-BAC: Available through X. William Yang. 5xFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live Lee et al., 2018 Yes
CV+mTrem2−/−5XFAD C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 Trem2, TREM2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V BAC transgenic mice carrying human TREM2 (common variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the common variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5xFAD mice. Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques surrounded by activated microglia. No data. Neurodegeneration-associated microglial activation markers elevated, compared with 5XFAD lacking TREM2. TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Song et al., 2018 Yes
R47H+mTrem2−/−5XFAD C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 Trem2, TREM2, APP, PSEN1 TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V BAC-transgenic mice carrying the human TREM2 (R47H variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5XFAD mice. Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant. No data. TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Song et al., 2018 Yes
Trem2-/-5XFAD, mTrem2-/-5XFAD  C57BL/6 -TREM2tm1cln; B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmja C57BL/6 Trem2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V 5XFAD mice were crossed with Trem2 KO mice. TREM2 KO: Targeted deletion of exons 3 and 4 of mouse Trem2. 5XFAD express two transgenes: 1) human APP with the Swedish, Florida and London mutations, containing the 5' untranslated region and driven by the mouse Thy1 promoter and 2) human PSEN1 with the M146L and L286V mutations driven by the mouse Thy1 promoter. Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes. No data. Trem2 KO: available through Marco Colonna. 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live Wang et al., 2015 Yes

8 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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E2FAD

Observed
  1. X
    Plaques at 17

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

  2. X
    Gliosis at 26

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

  3. X
    Synaptic Loss at 17

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

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

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

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

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

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

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E3FAD

Observed
  1. X
    Plaques at 17

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

  2. X
    Gliosis at 26

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

  3. X
    Synaptic Loss at 17

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

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

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

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

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

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

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E4FAD

Observed
  1. X
    Plaques at 17

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

  2. X
    Gliosis at 26

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

  3. X
    Synaptic Loss at 17

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

  4. X
    Cognitive Impairment at 8

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

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

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

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

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

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TREM2-BAC X 5xFAD

Observed
  1. X
    Plaques at 28

    Observed at 7 months, the youngest age examined.

  2. X
    Gliosis at 28

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

Absent
  • Cognitive Impairment at

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

No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

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

Amyloid plaques with plaque-associated microgliosis. Reduced plaque burden, altered microglial and plaque morphology, and less severe plaque-associated neuritic dystrophy, compared with 5xFAD.

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

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TREM2, humanized (common variant) X 5XFAD

Observed
  1. X
    Plaques at 34

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

  2. X
    Gliosis at 34

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

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Trem2, TREM2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques surrounded by activated microglia.

No data.

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TREM2, humanized (R47H) X 5XFAD

Observed
  1. X
    Plaques at 34

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

  2. X
    Gliosis at 34

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

Absent
No Data
  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Trem2, TREM2, APP, PSEN1 TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant.

No data.

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Trem2 KO (Colonna) x 5XFAD

Observed
  1. X
    Plaques at 16

    Plaques present by 4 months, the earliest age studied.

  2. X
    Neuronal Loss at 32

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

  3. X
    Gliosis at 16

    MIcrogliosis by 4 months, the earliest age studied.

Absent
No Data
  • Tangles at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Trem2, APP, PSEN1 APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes.

No data.

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