Research Models

Selected Results

6 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 (6)
APPNL-G-F/NL-G-F, AppNL-G-F Apptm3.1Tcs/Apptm3.1Tcs C57BL/6 APP APP KM670/671NL (Swedish), APP I716F (Iberian), APP E693G (Arctic) Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and three pathogenic mutations (Swedish, Beyreuther/Iberian, and Arctic). APP: Knock-In Alzheimer's Disease Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 6 months as measured by the Y maze. No overexpression of APP. Wild-type levels of AICD. Available through Takaomi Saido Saito et al., 2014 Yes
AppNL-G-F/MAPT double knock-in, AppNL-G-F/MAPT dKI C57BL/6J App, MAPT APP KM670/671NL (Swedish), APP I716F (Iberian), APP E693G (Arctic) AppNL-G-F mice (mouse App sequence modified to contain a humanized Aβ region and the Swedish, Iberian, and Arctic mutations linked to AD) were crossed with MAPT knock-in mice (entire genomic sequence of murine Mapt, from exon 1 to exon 14, replaced with the human MAPT gene from the ATG codon of exon 1 to the 3'-untranslated region). App: Knock-In; MAPT: Knock-In Alzheimer's Disease Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to AppNL-G-F. Deficits in the Y-maze test of working memory, similar to AppNL-G-F. Compared with AppNL-G-F mice, AppNL-G-F/MAPT double knock-in mice showed accelerated propagation of pathological tau species after AD-derived tau was injected into the mouse brain. Available through Takaomi Saido, RIKEN Center for Brain Science. Saito et al., 2019, Hashimoto et al., 2019 Yes
APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line Inbred C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana), APP E693G (Arctic) A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus. Cryopreserved. Contact Lennart Mucke Cheng et al., 2004 Yes
arcAbeta Origin: B6D2 F1 APP APP KM670/671NL (Swedish), APP E693G (Arctic) Human APP695 transgene containing the Swedish (K670N/M671L) and Arctic mutation (E693G) was generated by site-directed mutagenesis. APP: Transgenic Alzheimer's Disease At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma. Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze. Deficits in synaptic plasticity, LTP, and functional connectivity as measured by resting-state fMRI. Unknown Knobloch et al., 2007 Yes
B6CBA-Tg(Thy1.2-hAPParc) C57BL/6-CBA APP APP E693G (Arctic) Transgenic mice with human APP (isoform 695) bearing the Arctic APP mutation (E693G). APP: Transgenic Alzheimer's Disease Mild amyloid pathology with a relatively late onset, starting with intracellular Aβ, then diffuse extracellular Aβ deposits in the subiculum, expanding to interconnected brain regions such as retrosplenial granular cortex, thalamus, and mammillary bodies. Pathology more severe in females. Spatial learning and memory deficit in the Barnes maze test in heterozygous females mice at 15 months. Available through Annica Rönnbäck Rönnbäck et al., 2011 No
tg ArcSwe, APP-ArcSwe C57BL/6J APP APP KM670/671NL (Swedish), APP E693G (Arctic) Transgene with human APP (isoform 695) containing both the Arctic (E693G) and Swedish (KM670/671NL) mutations under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus. Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months. Tg-ArcSwe have reduced body weight compared with nontransgenic littermates. Available through Lars Nilsson Lord et al., 2006 Yes

5 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+.

APP NL-G-F Knock-in

Observed
  1. X
    Plaques at 9

    Aggressive amyloidosis; plaques develop in homozygous mice starting at 2 months with near saturation by 7 months. Aβ deposition at 4 months in heterozygous mice. Cortical and subcortical amyloidosis present.

  2. X
    Gliosis at 9

    Microglia and activated astrocytes accumulate with age starting around 2 months, especially around plaques in a manner concurrent with plaque formation.

  3. X
    Synaptic Loss at 17

    Reduction of synaptophysin and PSD95 immunoreactivities associated with Aβ plaques in both cortical and hippocampal areas.

  4. X
    Cognitive Impairment at 26

    Memory impairment in homozygous mice by 6 months of age as measured by the Y maze.

Absent
  • Tangles at

    Absent; although phosphorylated tau is elevated in dystrophic neurites around plaques.

  • Neuronal Loss at

    Absent.

No Data
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP I716F (Iberian), APP E693G (Arctic) APP: Knock-In Alzheimer's Disease

Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.

Memory impairment by 6 months as measured by the Y maze.

expand

AppNL-G-F/MAPT double knock-in

Observed
  1. X
    Plaques at 8

    Plaques observed at 2 months.

  2. X
    Gliosis at 16

    Astrogliosis and microgliosis observed by 4 months.

  3. X
    Cognitive Impairment at 52

    Deficits in the Y-maze test of working memory at 12 months of age.

Absent
  • Tangles at

    No neurofibrillary tangles observed up to 24 months of age.

  • Neuronal Loss at

    No neurodegeneration observed up to 24 months of age.

No Data
  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
App, MAPT APP KM670/671NL (Swedish), APP I716F (Iberian), APP E693G (Arctic) App: Knock-In; MAPT: Knock-In Alzheimer's Disease

Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to AppNL-G-F.

Deficits in the Y-maze test of working memory, similar to AppNL-G-F.

expand

Arc48 (APPSw/Ind/Arc)

Observed
  1. X
    Plaques at 9

    Parenchymal neuritic plaques by 2 months with prominent plaque deposition in the hippocampus by 3-4 months. Abundant mature thioflavin-S positive plaques with dystrophic neurites by 10-12 months (Cheng et al., 2007).

  2. X
    Gliosis at 13

    Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).

  3. X
    Cognitive Impairment at 13

    At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but were impaired in the ability to use extramaze cues to navigate to the hidden platform (Cheng et al., 2007).

Absent
  • Tangles at

    Absent.

No Data
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP V717F (Indiana), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20.

At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform.

expand

ArcAβ

Observed
  1. X
    Plaques at 39

    Between 9 and 15 months of age β-amyloid plaques became prominent. Plaques had a characteristic dense core morphology which differed from the cotton wool-like structure of plaques seen with the Swedish mutation alone (Knobloch et al., 2007).

  2. X
    Changes in LTP/LTD at 15

    LTP is severely impaired in slices from 3.5 and 7.5 month old mice. LTP and basal synaptic transmission were normal in slices from one month old mice (Knobloch et al., 2007).

  3. X
    Cognitive Impairment at 26
    Cognitive impairment measured from the age of 6 months in the Morris water maze and Y-maze, as well as in active avoidance behavior (Knobloch et al., 2007).
Absent
  • Tangles at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma.

Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze.

expand

Tg-ArcSwe

Observed
  1. X
    Plaques at 22

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

  2. X
    Gliosis at 26

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

  3. X
    Cognitive Impairment at 17

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

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP KM670/671NL (Swedish), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus.

Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months.

expand