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22 Models
20 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
-
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. |
5xFAD (C57BL6)
Observed
-
Plaques at 8
Amyloid plaques observed in hippocampus, cortex, thalamus, and spinal cord.
-
Neuronal Loss at 52
Approximate 40 percent loss of layer V pyramidal neurons at one year.
-
Gliosis at 8
Microgliosis and astrogliosis are associated with amyloid plaques; microgliosis is associated with vascular damage.
-
Synaptic Loss at 24
Spine density was reduced in pyramidal neurons in somatosensory and prefrontal cortices, but not in the hippocampi, of 5xFAD mice crossed with mice expressing yellow fluorescent protein (YFP mice), compared with mice expressing YFP alone.
-
Changes in LTP/LTD at 8
While spike-timing-dependent long-term potentiation was induced in layer V neurons from wild-type mice, the same stimulation protocol induced long-term depression in neurons from 5xFAD mice.
-
Cognitive Impairment at 24
Impairments of spatial working memory and reduced anxiety emerge between 3 and 6 months and worsen with age.
Absent
No Data
-
Tangles at
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 V. |
Age-dependent memory deficits, motor phenotype, and reduced anxiety. |
AAV-AD
Observed
-
Plaques at 128
Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection.
-
Changes in LTP/LTD at 40
Deficits in LTP as Schaffer collateral-CA1 synapse at 10 months (8 months post-injection). LTD similar to controls.
-
Cognitive Impairment at 40
AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training.
Absent
-
Gliosis at
No astrogliosis observed up to 30 months post-injection.
No Data
-
Tangles at
Immunostaining with monoclonal antibodies AT8 and AT100 suggests the presence of (pre)tangle-like structures 30 months post-injection.
-
Neuronal Loss at
No data.
-
Synaptic Loss at
No data.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M146L (A>C) | APP: Virus; PSEN1: Virus | Alzheimer's Disease | Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection. Anti-phospho-tau immunostaining suggests the presence of (pre)tangle-like structures. No astrogliosis seen up to 30 months post-injection. |
Compared with control rats at 8 months post-injection, AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training and less time in the center of the open field. |
AAV-sTREM2 5xFAD
Observed
-
Plaques at 28
When examined at 7 months of age, amyloid plaque burdens in the hippocampus and cortex of AAV-sTREM2 5xFAD mice were about half those of 5xFAD mice injected with control vector.
-
Gliosis at 28
The number of plaque-associated microglia was increased in AAV-sTREM2 5xFAD mice examined at 7 months of age.
-
Changes in LTP/LTD at 24
Long-term potentiation at Shaeffer collateral-CA1 synapses is impaired in 5xFAD mice. AAV-mediated over expression of sTREM2 rescued LTP in AAV-sTREM2 5xFAD mice.
-
Cognitive Impairment at 24
5xFAD mice show impaired learning and memory in the Morris water maze, but AAV-sTREM2 5xFAD mice performed as well as non-transgenic controls.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Synaptic Loss 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: Virus; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | AAV-mediated over expression of sTREM2 decreased amyloid plaque burdens and increased numbers of plaque-associated microglia in the brains of 5xFAD mice. |
5xFAD mice show impaired learning and memory in the Morris water maze, but AAV-sTREM2 5xFAD mice performed as well as non-transgenic controls. |
AD-BXD
Observed
-
Plaques at 24
Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, the earliest age examined. The extent of plaque deposition is strain-dependent.
-
Gliosis at 25
Strain-dependent gliosis by 6 months.
-
Cognitive Impairment at 60
In the AD-BXD population as a whole, transgenic mice performed similarly to non-transgenic littermates in a contextual fear-conditioning test at 6 months, but were impaired at 14 months. The age of onset and severity of impairment are strain-dependent.
Absent
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 |
|---|---|---|---|---|---|
| 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 | Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, although the extent of plaque deposition is strain-dependent. |
Transgenic AD-BXD mice exhibit cognitive deficits, assessed using contextual fear conditioning. The age of onset and severity of impairment are strain-dependent. |
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. |
APP(V717I)
Observed
-
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).
-
Gliosis at 43
GFAP, microglial activation, and other markers of brain inflammation are elevated by 10 months.
-
Changes in LTP/LTD at 26
Significant deficit in LTP in CA1 region of the hippocampus at 6 months.
-
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. |
APP(V717I) x PS1(A246E)
Observed
-
Plaques at 17
Plaques start in cortex, hippocampus and subiculum at 4-6 months.
-
Gliosis at 20
Elevated GFAP, microglial activation, and other markers of brain inflammation increase as of 4.5 months.
-
Changes in LTP/LTD at 26
Significant deficit in LTP in CA1 region of the hippocampus at 6 months.
-
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. |
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. |
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. |
Plcg2*M28L x 5xFAD
Observed
-
Plaques at 30
Diffuse and compact amyloid plaques observed in mice studied at 7.5 months of age. Higher plaque burdens than 5xFAD.
-
Gliosis at 31
Microgliosis observed in mice studied at 7.5 months of age.
-
Synaptic Loss at 32
Decreased basal synaptic transmission, lower frequencies and amplitudes of spontaneous excitatory postsynaptic currents and spontaneous inhibitory postsynaptic currents recorded in hippocampal CA1 region, compared with wild-type mice.
-
Changes in LTP/LTD at 33
Impaired LTP at Schaffer collateral-CA1 synapses, compared with wild-type.
-
Cognitive Impairment at 24
Deficits in working memory (decreased spontaneous alternation in the Y-maze), compared with wild-type.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| Plcg2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Plaque burdens in the cortex and subiculum were elevated in 5xFADM28L mice but microglia showed less interaction with plaques, compared with 5xFAD. |
Six-month-old 5xFADM28L and 5xFAD mice showed similar deficits in working memory, assessed in the Y-maze. |
Plcg2*P522R x 5xFAD
Observed
-
Plaques at 30
Diffuse and compact amyloid plaques observed in mice studied at 7.5 months of age. Lower plaque burdens than 5xFAD.
-
Gliosis at 31
Microgliosis observed in mice studied at 7.5 months of age.
Absent
-
Synaptic Loss at
No deficits in synaptic transmission—including basal synaptic transmission, frequencies and amplitudes of spontaneous excitatory postsynaptic currents and spontaneous inhibitory postsynaptic currents, and AMPA/NMDA current ratios—recorded in hippocampal CA1 region of 7.5-month-old mice.
-
Changes in LTP/LTD at
Normal LTP at Schaffer collateral-CA1 synapses at 7.5 months of age.
-
Cognitive Impairment at
Normal working memory (spontaneous alternation in the Y-maze) at 6 months of age.
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| Plcg2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Plaque burdens in the cortex and subiculum were lower in 5xFADP522R mice and microglia showed increased interaction with plaques, compared with 5xFAD. |
The PLCγ2 P522R variant protected against deficits in the Y-maze test of working memory in 5xFAD mice. |
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. |
TREM2-BAC X 5xFAD
Observed
-
Plaques at 28
Observed at 7 months, the youngest age examined.
-
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. |
Trem2-H157Y x 5xFAD
Observed
-
Plaques at 16
Decreased plaque burdens and densities in 5xFAD;Trem2H157Y/H157Y compared with 5xFAD;Trem2+/+ at 8.5 months, but genotypes similar at 4 months.
-
Gliosis at 16
Decreased microgliosis and astrogliosis in 5xFAD;Trem2H157Y/H157Y compared with 5xFAD;Trem2+/+ at 8.5 months, but genotypes similar at 4 months.
Absent
-
Synaptic Loss at
Cortical levels of synaptophysin and PSD95 did not differ between genotypes at 8.5 months.
No Data
-
Tangles at
No data.
-
Neuronal 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 | TREM2 H157Y, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Age-dependent effects on amyloid-β pathology and gliosis. At 4 months, plaque burdens, microgliosis, and astrogliosis were similar among genotypes. By 8.5 months, amyloid burdens, microgliosis, and astrogliosis were reduced in homozygous carriers of the H157Y variant, compared with 5xFAD mice homozygous for wild-type Trem2. |
Unknown. |
TREM2, humanized (R47H) X 5XFAD
Observed
-
Plaques at 34
Plaques observed in 8.5-month-old mice, the only age reported thus far.
-
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. |
Trem2 KO (Colonna) x 5XFAD
Observed
-
Plaques at 16
Plaques present by 4 months, the earliest age studied.
-
Neuronal Loss at 32
Loss of cortical layer V neurons by 8 months, the earliest age studied.
-
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. |