Research Models

Selected Results

4 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 (4)
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

4 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.

expand

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.

expand

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.

expand

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.

expand