Research Models
Alzheimer's Disease
There is a large ongoing effort to characterize animal models of AD in order to better understand disease pathophysiology as well as to identify models suitable for investigating potential therapeutics. By organizing information about the characterization of selected AD models, this resource conveys what is known about each one and facilitates comparison between them.
230 Models
175 Visualizations
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+.
3xTg
Observed
-
Plaques at 26
Extracellular Aβ deposits by 6 months in the frontal cortex, predominantly layers 4 and 5 and progress with age (Oddo et al., 2003).
-
Tangles at 52
By 12 months extensive tau immunoreactivity in CA1 neurons of the hippocampus, particularly pyramidal neurons, later in the cortex. No tau pathology at 6 months (Oddo et al., 2003).
-
Gliosis at 30
Increased density of GFAP immunoreactive astrocytes and IBA-1 immunoreactive microglia compared with wild-type mice at 7 months (Caruso et al., 2013). Development of gliosis may occur earlier.
-
Changes in LTP/LTD at 26
By 6 months decreased LTP compared with wild type controls. Impairment in basal synaptic transmission. No change at 1 month of age (Oddo et al., 2003).
-
Cognitive Impairment at 17
Cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Aβ in the hippocampus and amygdala, but plaques and tangles are not yet apparent (Billings et al., 2005).
Absent
No Data
-
Neuronal Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Psen1, APP, MAPT | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V | Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic | Alzheimer's Disease | Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. |
Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task. |
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. |
A7 APP transgenic
Observed
-
Plaques at 39
These mice develop progressive amyloid deposition in the cerebral cortex by 9-12 months. By 21 months of age amyloid pathology is extensive.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP T714I (Austrian) | APP: Transgenic | Alzheimer's Disease | Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months. |
Unknown. |
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. |
AAV-sTREM2 PS19
Observed
-
Synaptic Loss at 28
AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.
-
Changes in LTP/LTD at 29
LTP at Shaeffer collateral-CA1 synapses was slightly enhanced in hippocampal slices from 7-month-old AAV-sTREM2 PS19 mice, compared with PS19 mice who had received control vector.
-
Cognitive Impairment at 30
AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze.
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
TREM2, MAPT | MAPT P301S | TREM2: Virus; MAPT: Transgenic | Frontotemporal Dementia, Alzheimer's Disease | AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice. |
AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze. |
Abca7*A1527G/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Abca7, APOE, Trem2 | TREM2 R47H | Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Abca7 KO/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Abca7, APOE, Trem2 | TREM2 R47H | Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
ADanPP
Observed
-
Plaques at 9
Vascular amyloid deposits and punctate parenchymal aggregates first occur in the hippocampus and increase with age, spreading throughout the brain, including the cortex, amygdala, thalamus, and brainstem in hemizygous mice.
-
Gliosis at 17
Astrogliosis and microgliosis increase with age and increasing ADan-amyloid deposition.
-
Cognitive Impairment at 78
The only ages tested were 6 months and 18-20 months. Mice 18-20 months of age exhibited both motor and spatial learning defects in the Morris water maze, and increased anxiety in the open field test. No impairments were observed in 6 month-old mice.
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 |
---|---|---|---|---|---|
ITM2B (BRI2) | BRI2: Familial Danish Dementia (FDD) duplication | ITM2B (BRI2): Transgenic | Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy | ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present. |
Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype. |
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. |
APOE2 Knock-In, floxed (CureAlz)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE | APOE: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
APOE2 Knock-In (JAX)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE | APOE: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
APOE3 Knock-In, floxed (CureAlz)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE | APOE: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
APOE3 Knock-In (JAX)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE | APOE: Knock-In | Alzheimer's Disease | No data. |
No data. |
APOE3 Knock-In (Lamb)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE | APOE: Knock-In | Alzheimer's Disease, Traumatic Brain Injury | Unknown. |
Unknown. |
APOE4 Knock-In, floxed (CureAlz)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE | APOE: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
APOE4 Knock-In (JAX)
Observed
Absent
-
Cognitive Impairment at
At 2 and 12 months of age, APOE4 KI mice perform similarly to wild-type mice in tests of locomotor activity, motor coordination, and working memory.
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APOE | APOE: Knock-In | Alzheimer's Disease | No data. |
No data. |
APP21
Observed
-
Neuronal Loss at 76
Necrotic neurons in hippocampus and cortex of female rats.
-
Gliosis at 64
Activated (MHCII-positive) microglia present in white matter tracts at 15 months.
-
Cognitive Impairment at 12
Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.
Absent
-
Plaques at
Do not spontaneously develop amyloid pathology, but can serve as hosts for exogenously seeded amyloid deposits.
No Data
-
Tangles at
“Flame-shaped” profiles in hippocampal neurons of 18- to 19-month-old female rats revealed by hematoxylin-and-eosin-staining.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | APP: Transgenic | Alzheimer's Disease | No plaques to 30 months of age. Necrotic neurons in hippocampus and cortex by 19 months, in females; neuron loss not observed in cortices of 19-month males. |
Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age. |
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. |
APP23 x PS1-R278I
Observed
-
Plaques at 26
By 6 months of age amyloid plaques accumulate in the cortex and hippocampus. A high percentage of plaques are thioflavin-S –positive cored plaques.
-
Gliosis at 39
Astrocytosis in the vicinity of plaques in the hippocampus and cortex by 9 months.
-
Cognitive Impairment at 13
Short-term memory deficits are apparent by 3 to 4 months as measured by the Y maze.
Absent
-
Tangles at
Not observed.
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 | PSEN1 R278I | APP: Transgenic; PSEN1: Knock-In | Alzheimer's Disease | Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques. |
Short-term memory deficits apparent by 3-4 months as measured by the Y maze. |
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. |
APPDutch
Observed
-
Gliosis at 126
Microgliosis develops after the onset of CAA pathology and is prominent in areas adjacent to amyloid-laden vessels. There is also widespread activation of astrocytes in neocortical regions affected by CAA. These changes have been reported at 29 months of age, although the actual onset of gliosis may occur earlier than has been examined.
Absent
-
Plaques at
No plaques are observed, but CAA develops at 22-24 months.
-
Tangles at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
-
Cognitive Impairment at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP E693Q (Dutch) | APP: Transgenic | Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease | Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed. |
Unknown. |
APP E693Δ-Tg (Osaka)
Observed
-
Neuronal Loss at 104
Neuronal loss, as measured by NeuN staining, was observed in the CA3 region of the hippocampus at 24 months of age. Neuronal loss was not detected in the cerebral cortex at this time.
-
Gliosis at 52
At 12 months of age, microgliosis is seen in transgenic mice, as measured by the presence of Iba-1 staining in the hippocampus and cortex. Astrocytosis, as measured by GFAP-reactivity, increased starting around 18 months of age in these regions.
-
Synaptic Loss at 34
Starting around eight months of age, transgenic mice exhibit a decrease in synaptic density in the CA3 region of the hippocampus as measured by synaptophysin staining.
-
Changes in LTP/LTD at 35
By eight months of age, transgenic mice exhibit reduced short term plasticity as measured by paired-pulse facilitation in addition to reduced LTP as elicited by high frequency stimulation to the perforant pathway.
-
Cognitive Impairment at 36
By 8 months of age, transgenic mice exhibit memory impairment in the Morris water maze compared to mice expressing equivalent levels of wild-type human APP.
Absent
-
Plaques at
Extracelluar amyloid plaques are not observed out to 24 months; however, Aβ accumulates within neurons of the hippocampus and cerebral cortex starting around eight months of age.
-
Tangles at
Overt tangle pathology is not observed out to 24 months of age, but abnormal tau phosphorylation is observed starting around eight months of age.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP E693del (Osaka) | APP: Transgenic | Alzheimer's Disease | Age-dependent accumulation of Aβ oligomers within hippocampal and cortical neurons, but negligible deposits of extracellular amyloid. Abnormal tau phosphorylation, but no overt tangle pathology. Synaptic loss and gliosis in hippocampus and cerebral cortex. Late neuronal loss in the CA3 region of the hippocampus. |
Memory impairment by eight months as measured by the Morris water maze. Specifically, reduced spatial reference memory in the Morris water maze compared to mice expressing comparable levels of wild-type human APP. |
App knock-in (humanized Aβ)
Observed
Absent
-
Plaques at
None observed at 3 months.
-
Tangles at
None observed at 3 months.
-
Neuronal Loss at
None observed at 3 months.
No Data
-
Gliosis 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 |
---|---|---|---|---|---|
App | App: Knock-In | Alzheimer's Disease | No plaques, neurofibrillary tangles, or neuron loss observed at three months, the oldest age reported. |
Unknown. |
App knock-in (humanized Aβ)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
App | App: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
App knock-in (humanized Aβ) (Leuven)
Observed
Absent
-
Plaques at
No plaques observed up to 2 years of age.
-
Tangles at
No tangles observed up to 2 years of age.
No Data
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
App | App: Knock-In | Alzheimer's Disease | No plaques or tangles were observed up to two years of age. |
Unknown. |
App knock-in (humanized Aβ) (Leuven); Psen1 knock-in (M139T)
Observed
Absent
-
Plaques at
No plaques observed up to 2 years of age.
-
Tangles at
No tangles observed up to 2 years of age.
No Data
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
App, Psen1 | PSEN1 M139T | App: Knock-In; Psen1: Knock-In | Alzheimer's Disease | No plaques or tangles were observed up to 2 years of age. |
Unknown. |
App knock‐in (Icelandic mutation and humanized Aβ)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
App | APP A673T (Icelandic) | App: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
App knock‐in (Swedish mutation and humanized Aβ)
Observed
Absent
-
Plaques at
None observed at 3 months.
-
Tangles at
None observed at 3 months.
-
Neuronal Loss at
None observed at 3 months.
No Data
-
Gliosis 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 |
---|---|---|---|---|---|
App | APP K670_M671delinsNL (Swedish) | App: Knock-In | Alzheimer's Disease | No plaques, neurofibrillary tangles, or neuron loss observed at 3 months, the oldest age reported. |
Unknown. |
App KO/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, App, Trem2 | TREM2 R47H | APOE: Knock-In; App: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
APP NL-F Knock-in
Observed
-
Plaques at 26
Homozygotes develop amyloid plaques starting at 6 months in the cortex and hippocampus. Heterozygotes develop amyloidosis after 24 months. Plaques contained Aβ1-42 and pyroglutamate Aβ (Aβ3(pE)-42); Aβx-40 was a minor species.
-
Gliosis at 26
Microglia and activated astrocytes accumulate with age, starting around 6 months of age, concurrent with plaque formation.
-
Synaptic Loss at 39
Reduced synaptophysin and PSD95 immunoreactivities associated with Aβ plaques at 9-12 months.
-
Cognitive Impairment at 78
Memory impairment in homozygous mice at 18 months as measured by the Y maze test. APPNL/NL mice (with Swedish mutation only) were unimpaired at this age. No significant deficit was seen in the Morris water maze at 18 months.
Absent
-
Tangles at
Absent; although elevated levels of phosphorylated tau are observed 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 K670_M671delinsNL (Swedish), APP I716F (Iberian) | APP: Knock-In | Alzheimer's Disease | Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. |
Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. |
APP NL-G-F Knock-in
Observed
-
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.
-
Gliosis at 9
Microglia and activated astrocytes accumulate with age starting around 2 months, especially around plaques in a manner concurrent with plaque formation.
-
Synaptic Loss at 17
Reduction of synaptophysin and PSD95 immunoreactivities associated with Aβ plaques in both cortical and hippocampal areas.
-
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 K670_M671delinsNL (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. |
App NL-G-F Knock-in Rat
Observed
-
Plaques at 4
Amyloid plaques apparent as early as 1 month in homozygous knock-ins, 4 months in heterozygotes. Amyloid pathology progresses more rapidly in females than males.
-
Neuronal Loss at 52
Reduced brain weight, fewer neurons in the hippocampus and cortex, and enlarged lateral ventricles seen at 12 months.
-
Gliosis at 24
Astrogliosis and microgliosis, particularly pronounced around amyloid plaques, were observed in homozygous knock-in rats at 6 months of age. Gliosis was also seen in year-old heterozygotes.
-
Synaptic Loss at 24
Decreased levels of the presynaptic marker synaptophysin and the postsynaptic marker PSD-95 in knock-in rats. Quantitative electron microscopy showed reductions in synaptic density, area, and perimeters in the hippocampus, entorhinal cortex and prefrontal cortex of knock-in brains.
-
Cognitive Impairment at 20
Deficits in the Morris Water Maze task and a paired associate learning task as early as 5 and 7 months of age, respectively.
Absent
-
Tangles at
No neurofibrillary tangles through 22 months of age, but increases in tau phosphorylation, aggregation, and conformational changes.
No Data
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
App | APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP I716F (Iberian) | App: Knock-In | Alzheimer's Disease | Amyloid plaques apparent as early as 1 month in homozygous knock-ins. No neurofibrillary tangles through 22 months of age, but increases in tau phosphorylation, aggregation, and conformational changes. Astrogliosis, microgliosis, synapse and neuron loss. |
Deficits in the Morris Water Maze task and a paired associate learning task as early as 5 and 7 months of age, respectively. |
AppNL-G-F/MAPT double knock-in
Observed
-
Plaques at 8
Plaques observed at 2 months.
-
Gliosis at 16
Astrogliosis and microgliosis observed by 4 months.
-
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 K670_M671delinsNL (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. |
APPPS1
Observed
-
Plaques at 6
Aβ deposition begins at 6 weeks of age in the cortex and 3-4 months of age in the hippocampus (Radde et al., 2006).
-
Neuronal Loss at 74
Global neuron loss is not observed, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuronal density in 17-month old animals (Rupp et al., 2011).
-
Gliosis at 6
Activated microglia around Aβ deposits at 6 weeks as well as increased astrogliosis (Radde et al., 2006). Levels of CCL2 and TNFα increase at later ages (Lee et al., 2010).
-
Synaptic Loss at 10
Dendritic spine loss around plaques reported to begin approximately 4 weeks after plaque formation and continue for several months (Bittner et al., 2012).
-
Changes in LTP/LTD at 35
Hippocampal CA1 LTP normal at 4.5 months of age, but impaired at 8 and 15 months of age (Gengler et al., 2010).
-
Cognitive Impairment at 30
Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006).
Absent
-
Tangles at
Phosphorylated tau-positive neuritic processes around plaques have been observed, but no mature tangles (Radde et al., 2006).
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 L166P | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.
|
Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months. |
APP+PS1
Observed
-
Plaques at 76
Abundant plaques in hippocampus and subiculum, scattered plaques in cortex.
-
Neuronal Loss at 76
Necrotic neurons in hippocampus and cortex.
-
Cognitive Impairment at 40
Deficits in Barnes maze at 10 months.
Absent
No Data
-
Tangles at
No data.
-
Gliosis 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 V717F (Indiana), PSEN1 L166P | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age. |
Deficits in Barnes maze by 10 months of age. |
APP/PS1/rTg21221
Observed
-
Plaques at 35
Cortical plaques observed between 8-10 months. Plaques larger than in control mice not expressing human tau.
-
Neuronal Loss at 36
Neuronal loss observed adjacent to plaques relative to more distal areas.
-
Gliosis at 37
Increased astrocytosis adjacent to plaques relative to more distal areas.
-
Synaptic Loss at 40
Decreased synapse density adjacent to plaques relative to more distal areas.
Absent
-
Tangles at
No tangles. Aggregates of misfolded and phosphorylated tau observed between 8-10 months.
No Data
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1, MAPT | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic | Alzheimer's Disease | Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed. |
No data. |
AppSAA Knock-in
Observed
-
Plaques at 16
Amyloid plaques seen in AppSAA homozygous mice from 4 months of age and heterozygous mice at 16 months of age.
-
Gliosis at 16
Plaque-associated microgliosis observed by 4 months of age.
Absent
-
Tangles at
AT8-positive dystrophic neurites, but no neurofibrillary tangles, detected in AppSAA homozygous mice at 8 months of age.
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 |
---|---|---|---|---|---|
App | APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP T714I (Austrian) | App: Knock-In | Alzheimer's Disease | Homozygotes: Amyloid plaques and plaque-associated microgliosis from 4 months of age; cerebral amyloid angiopathy and dystrophic neurites from 8 months of age. Heterozygotes: Amyloid plaques at 16 months of age. |
Unknown. |
APPsw/0; Pdgfrβ+/-
Observed
-
Plaques at 39
By 9 months of age APPsw/0;Pdgfrβ+/- mice have an elevated plaque load in the cortex and hippocampus compared with age matched APPsw/0;Pdgfrβ+/+. littermates. They also have extensive cerebral amyloid angiopathy.
-
Neuronal Loss at 39
Progressive neuronal degeneration including reduced neurite density and reduced neuronal number in the cortex and hippocampus of APPsw/0; Pdgfrβ+/- mice at at nine months compared to age-matched APPsw/0; Pdgfrβ+/+ littermates.
-
Cognitive Impairment at 41
At nine months, APPsw/0;Pdgfrβ+/- mice perform poorly on several hippocampal-dependent behavioral tests including burrowing, nest construction, and novel object recognition, compared with age-matched APPsw/0;Pdgfrβ+/+ littermates.
Absent
No Data
-
Tangles at
Although mature neurofibrillary tangles were not observed by 9 months (the oldest age assessed), the mice develop significant tau pathology, including tau hyperphosphorylation in cortical and hippocampal neurons. Pre-tangle pathology is observed, including neuronal caspase-cleaved tau, and conformational changes as indicated by the conformation-specific antibody MC1.
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PDGFRB | APP K670_M671delinsNL (Swedish) | APP: Transgenic; PDGFRB: Knock-Out | Alzheimer's Disease | Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus. |
Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition. |
APPSwDI x NOS2 Knock-out
Observed
-
Plaques at 49
Aβ deposits by 52 weeks. Particularly dense Aβ immunoreactivity in the subiculum and thalamus, including in the cerebral microvessels (Wilcock et al., 2008).
-
Tangles at 49
Extensive tau pathology by 52 weeks, including intraneuronal aggregates of hyperphosphorylated tau. Increased phosphorylated tau in bigenic mice compared to APPSwDI mice (Wilcock et al., 2008).
-
Neuronal Loss at 52
Significant neuron loss by 52 weeks in the hippocampus and subiculum, especially of neuropeptide Y neurons. Numerous Fluoro-Jade C+ neurons: 30% loss in the hippocampus, 35% loss in the subiculum (Wilcock et al., 2008).
-
Cognitive Impairment at 53
Impairments in spatial memory by 52-56 weeks as measured by the radial arm maze and the Barnes maze. Bigenic mice more impaired than APPSwDI (Wilcock et al., 2008).
Absent
No Data
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, NOS2 | APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) | APP: Transgenic; NOS2: Knock-Out | Alzheimer's Disease | Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone. |
Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks. |
APP(Swedish) (R1.40)
Observed
-
Plaques at 59
By 13.5 months homozygous mice develop both parenchymal and vascular amyloid deposits which first appear in the frontal cortex. No Aβ deposition at 5 months (Lehman et al., 2003).
-
Gliosis at 61
Reactive astrocytes and microglia in 14-16 month old animals (Kulnane et al., 2001).
Absent
-
Tangles at
No mature tangles, but some changes in phosphorylated tau.
-
Changes in LTP/LTD at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
-
Cognitive Impairment at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish) | APP: Transgenic | Alzheimer's Disease | By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months. |
Unknown. |
APPSwe (line C3-3)
Observed
-
Plaques at 104
Some plaque formation at advanced age (24-26 months) (Savonenko et al., 2003).
Absent
-
Cognitive Impairment at
Normal reference and working memory up to 12-14 months on congenic background (Savonenko et al., 2003).
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish) | APP: Transgenic | Alzheimer's Disease | Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age. |
Congenic animals showed normal reference and working memory up to 12-14 months. |
APPSwe/PSEN1(A246E)
Observed
-
Plaques at 39
By 9 months of age, amyloid plaques develop in the hippocampus and subiculum, later extending to the cortex (Borchelt et al., 1997). The striatum and thalamus are relatively spared out to 18 months of age. Amyloid pathology is more severe in female mice, with a greater amyloid burden measured at 12 and 17 months of age (Wang et al., 2003).
-
Gliosis at 52
By one year of age, reactive gliosis is observed in the cortex and hippocampus and is associated with dystrophic neurites (Borchelt et al., 1997).
-
Cognitive Impairment at 48
Age-associated cognitive impairment, as measured by the Morris water maze, was observed in 11 to 12-month-old males. Both acquisition and retention were impaired. No impairment at 3-4 months of age. At both time points mice performed normally on a position discrimination task in the T-maze (Puoliväli et al., 2002).
Absent
-
Tangles at
Not observed.
-
Neuronal Loss at
There was no difference in neuronal numbers in the cingulate cortex compared with wild-type mice (Xiang et al., 2002).
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), PSEN1 A246E | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus. |
Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task. |
APPSwe/PSEN1dE9 (C3-3 x S-9)
Observed
-
Plaques at 26
Plaques are present in the hippocampus and cortex by 6 months of age.
-
Cognitive Impairment at 78
Age-related cognitive deficits. Episodic memory appears to be more sensitive than reference memory. No differences at 6 months of age, but detectable at 18 months (Savonenko et al., 2005).
Absent
-
Tangles at
Not observed.
No Data
-
Neuronal Loss at
No data.
-
Gliosis 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), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers. |
Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months. |
APPswe/PSEN1dE9 (C57BL6)
Observed
-
Plaques at 16
Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months.
-
Gliosis at 17
Plaque-associated astrogliosis and microgliosis are evident by 4 and 8 months, respectively.
-
Synaptic Loss at 18
Synapse loss in the hippocampus occurs by 4 months.
-
Cognitive Impairment at 40
Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age.
Absent
-
Tangles at
Not observed.
-
Neuronal Loss at
Neuron loss has not been observed in mice up to 12 months of age.
No Data
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months. Gliosis and dystrophic neurites are associated with plaques. Amyloid angiopathy has been observed in the retina. |
Hyperactivity is apparent by 6 months. Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age. |
APPswe/PSEN1dE9 (line 85)
Observed
-
Plaques at 26
Occasional Aβ deposits can be found by 6 months, with abundant plaques in the hippocampus and cortex by 9 months (Jankowsky et al., 2004) and a progressive increase in plaques up to 12 months (Garcia-Alloza et al., 2006).
-
Neuronal Loss at 35
Neuronal loss observed adjacent to plaques relative to more distal areas.
-
Gliosis at 26
Minimal astrocytosis at 3 months; significant astrocytosis by 6 months, especially in areas around plaques. Extensive GFAP+ staining at 15 months and later throughout the cortex (Kamphuis et al., 2012).
-
Synaptic Loss at 17
In the B6 congenic mice, age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and Homer immunoreactivity in the hippocampus by 4 months (Hong et al., 2016).
-
Changes in LTP/LTD at 13
Transient long-term potentiation (t-LTP) is reduced by 3 months. The degree of impairment is not related to age from 3 to 12 months (Volianskis et al., 2008).
-
Cognitive Impairment at 52
Impairment in the Morris water maze at 12 months, specifically during acquisition of the hidden platform sub-task and the probe trial, but not in the visible platform test (Lalonde et al., 2005). At 13 months the mice commit more errors in the Morris water maze, but not at 7 months (Volianskis et al., 2008).
Absent
-
Tangles at
Not observed.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity. |
Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing). |
APP(V642I)KI
Observed
-
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. |
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. |
Arc48 (APPSw/Ind/Arc)
Observed
-
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).
-
Gliosis at 13
Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).
-
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 K670_M671delinsNL (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. |
ArcAβ
Observed
-
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).
-
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).
-
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 K670_M671delinsNL (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. |
ARTE10
Observed
-
Plaques at 13
Robust and reliable plaque pathology as early as 3 months in homozygotes, 5 months in hemizygotes. Plaques start in the anterior neocortex and subiculum, spreading to other brain regions (e.g. hippocampus, thalamus, amygdala). Congophilic dense-core plaques are abundant, with lower levels of diffuse plaques and some cerebral amyloid angiopathy.
-
Gliosis at 22
Glial activation, including reactive astrocytes and activated microglia, is present in areas around plaques by 5 months of age in homozygous animals, later in hemizygotes.
-
Synaptic Loss at 13
Decreased expression of synaptophysin mRNA in the brain by 3-4 months of age in both hemizygous and homozygous animals.
-
Cognitive Impairment at 52
Select, paradigm-dependent, deficits in learning and memory, especially episodic memory, by 12 months in homozygous and hemizygous mice.
Absent
-
Tangles at
No tangles or neuropil threads, but some hyperphosphorylated tau by eight months in dystrophic neurites.
-
Neuronal Loss at
Outright neuronal loss has not been documented, but substantial degeneration of dendritic arbors occurs by 10-14 months of age in hippocampal neurons.
No Data
-
Changes in LTP/LTD at
Unknown; however, hippocampal neurons exhibit substantial changes in electrophysiological properties by 10-14 months of age, including hyperexcitability in the form of increased firing of action potentials and a more efficient transition from solitary firing to bursting.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146V | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches. |
Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months. |
Atg16LΔWD
Observed
-
Neuronal Loss at 104
Apparent neuron loss in hippocampi of 2-year-old mice (fewer neurons, increased levels of cleaved caspase-3, and increased numbers of TUNEL-positive neurons).
-
Gliosis at 104
Microgliosis in the hippocampi of 2-year-old mice.
-
Changes in LTP/LTD at 104
Impaired long-term potentiation at CA3-CA1 synapses.
-
Cognitive Impairment at 104
Deficits in the sucrose preference test, spontaneous alternation in the Y-maze, and novel object recognition test.
Absent
-
Plaques at
Intracellular and extracellular Aβ deposits, but no dense-core plaques, in 2-year-old mice.
No Data
-
Tangles at
No data.
-
Synaptic Loss at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Atg16l1 | Atg16l1: Knock-Out | Alzheimer's Disease | Intracellular and extracellular Aβ deposits, but no dense-core plaques. Microgliosis and neuron loss in 2-year-old mice. |
Deficits in the sucrose-preference test, spontaneous alternation in the Y-maze, and novel object recognition test. |
BACE1 cKO (Hu, Yan) X 5xFAD
Observed
-
Plaques at 11
Accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.
-
Gliosis at 11
Reactive astrocytes and microglia accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.
-
Changes in LTP/LTD at 40
Deficit in LTP at Schaffer collateral–CA1 synapses, but less severe than in control 5xFAD mice.
Absent
-
Cognitive Impairment at
Cued and contextual fear conditioning normal, tested at eight to 10 months of age.
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Synaptic Loss at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Bace1, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter. |
Normal contextual and cued fear conditioning, tested at 8 to 10 months of age. |
Bace1 conditional knock-out (adult, whole body) (Vassar)
Observed
Absent
-
Changes in LTP/LTD at
LTP at Schaffer collateral–CA1 synapses was similar in slices obtained from 12-month BACE1-deficient and control mice.
-
Cognitive Impairment at
Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning when tested at 9 months of age.
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Bace1 | Bace1: Conditional Knock-out | Alzheimer's Disease | Defects in axonal organization. |
Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations. |
BACE1 conditional knock-out (Hu, Yan)
Observed
-
Changes in LTP/LTD at 40
Long-term potentiation at Schaffer collateral–CA1 synapses impaired in slices obtained from 10- to 12-month-old mice.
Absent
-
Plaques at
Not observed.
-
Tangles at
Not observed.
-
Neuronal Loss at
Not observed.
-
Gliosis at
No astrogliosis at 1-2 months.
-
Cognitive Impairment at
Contextual and cued fear conditioning normal at 8-10 months.
No Data
-
Synaptic Loss at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Bace1 | Bace1: Conditional Knock-out | Alzheimer's Disease | No gross morphological changes observed. |
BACE1-deficient mice and Bace1fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age. |
Bace1 conditional knock-out (neonatal, forebrain) (Vassar)
Observed
-
Cognitive Impairment at 24
Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning.
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Bace1 | Bace1: Conditional Knock-out | Alzheimer's Disease | Hypomyelination and defects in axon organization. |
Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments. |
Bace1 conditional knockout (Tesco)
Observed
-
Changes in LTP/LTD at 60
Deficit in long-term potentiation at Schaffer collateral–CA1 synapses in slices from 14-month-old animals that had received tamoxifen between 8 and 12 weeks of age.
Absent
-
Cognitive Impairment at
Animals that had received tamoxifen between 8 and 12 weeks of age were tested at 4–5 or 12–14 months. Tamoxifen-treated mice performed similarly to vehicle-treated controls in the Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition tests.
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Bace1 | Bace1: Conditional Knock-out | Alzheimer's Disease | None observed: hippocampal mossy fiber organization and sciatic-nerve myelination were normal. |
Performed similarly to controls in a battery of tests (Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition task). |
BRI-Aβ42 (BRI2-Aβ42)
Observed
-
Plaques at 13
Detergent-insoluble amyloid-β and cored plaques as early as three months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices by 12 months. Extensive congophillic amyloid angiopathy.
-
Gliosis at 13
Plaque-associated reactive gliosis as measured by GFAP immunostaining.
Absent
-
Tangles at
Absent.
-
Neuronal Loss at
Absent.
-
Cognitive Impairment at
On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss. |
On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid. |
CAST.APP/PS1
Observed
-
Plaques at 32
Thioflavin S-positive amyloid plaques are present in the cortex and hippocampus by 8 months of age, with more severe plaque pathology in females than in males.
-
Neuronal Loss at 34
Compared with their non-transgenic littermates, CAST.APP/PS1 mice have fewer neurons in area CA1 of the hippocampus. Cortical neuron numbers do not differ between the genotypes.
-
Gliosis at 33
Plaque-associated microgliosis observed by 8 months.
-
Cognitive Impairment at 31
Deficits in short-term memory by 8 months in males (data from females unavailable).
Absent
-
Tangles at
Not observed.
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), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in hippocampal area CA1. |
Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in males (data from females is not available, as wild-type females are unable to perform this test). |
Ceacam1 KO/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, Ceacam1, Trem2 | TREM2 R47H | APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Clasp2*L163P/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Clasp2, APOE, Trem2 | TREM2 R47H | Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
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. |
E4FAD
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
Decreased protein levels of PSD95 and NMDA receptor subunits by 4 months.
-
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. |
hAbeta/APOE4/Trem2*R47H (LOAD2)
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, APP, Trem2 | TREM2 R47H | APOE: Knock-In; APP: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
hAbeta-loxP-KI
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APP | APP: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
hAβ-KI
Observed
-
Synaptic Loss at 78
Fewer synaptophysin-immunoreactive puncta, but similar numbers of PSD95-immunoreactive puncta, in knock-in mice compared with wild-type mice.
-
Changes in LTP/LTD at 78
Impaired theta-burst-induced LTP at Schaffer collateral-CA1 synapses, by 18 months of age.
-
Cognitive Impairment at 40
Differed from wild-type mice in the contextual fear conditioning test by 10 months of age and in the novel object recognition task by 14 months.
Absent
-
Plaques at
No plaques observed through 22 months of age, using immunohistochemical, thioflavin-S or Congo red stains.
-
Neuronal Loss at
Neuron numbers in hippocampal CA1 were similar in 22-month hAβ-KI and wild-type mice, although hippocampal volume was decreased in the knock-in mice.
-
Gliosis at
Neither microgliosis nor astrogliosis was observed through 22 months of age.
No Data
-
Tangles at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
App | App: Knock-In | Alzheimer's Disease | No amyloid plaques observed through 22 months of age. Accelerated formation of OC-immunoreactive and Periodic Acid Schiff-positive granules. |
Differed from wild-type mice in the contextual fear conditioning test by 10 months of age and in the novel object recognition task by 14 months. |
hCR1 KI on APOE4/Trem2
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Cr2, CR1, CR2, APOE, Trem2 | TREM2 R47H | Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
htau
Observed
-
Tangles at 39
Aggregated tau and paired helical filaments detectable at nine months by immunoelectron microscopy, although paired helical filaments of aggregated insoluble tau can be isolated from brain tissue as early as two months. Tau first redistributes from axons to cell bodies. Hyperphosphorylated tau begins to accumulate by six months, and increases further by 13 and 15 months (Andorfer et al., 2003).
-
Neuronal Loss at 43
Decrease in cortical thickness and reduced cell number between 10 and 14 months of age. Increased ventricle size increased from age eight months to 18 months. Decrease in the thickness of the corpus callosum (Andorfer et al., 2005).
-
Changes in LTP/LTD at 52
In hippocampal slices, LTP induced by high frequency stimulation (HFS) was normal at four months but abolished by 12 months. LTP induced by theta burst stimulation (TBS) was normal at both ages. Paired-pulse ratio (PPR) was unaffected at four months, but increased at 12 months compared with controls, suggesting a decrease in probability of transmitter release (Polydoro et al., 2009).
-
Cognitive Impairment at 26
Abnormal spatial learning in six-month-old mice compared with control mice (Phillips et al., 2011). Normal object recognition and spatial learning and memory by MWM at four months, but deficits by 12 months (Polydoro et al., 2009). Impaired burrowing relative to control mice occurs by four months (Geiszler et al., 2016).
Absent
No Data
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT: Knock-Out; MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia | Age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately thioflavin-S positive neurofibrillary tangles. Pathology most severe in neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some neuronal loss. |
Normal object-recognition memory and spatial learning/memory (as assessed by the Morris Water Maze) at four months, but impaired at 12 months (Polydoro et al., 2009). |
hTau-A152T
Observed
-
Neuronal Loss at 87
Neuron loss in the hippocampus was observed by 20 months.
-
Gliosis at 17
Astrocytosis, but no differences in microglia.
-
Cognitive Impairment at 74
In the Morris water maze, performance was impaired after 17 months of age. Nest building was impaired at 10-14 months. Social interaction, anxiety, exploratory behavior, and motor functions were unaltered.
Absent
-
Tangles at
Abnormal accumulations of soluble tau were observed, but not tangles or tangle-like structures.
-
Changes in LTP/LTD at
Unchanged at 20 months.
No Data
-
Plaques at
No data.
-
Synaptic Loss at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT A152T | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus. |
Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal. |
hTau-AT (hTau40-AT)
Observed
-
Tangles at 13
Tangles in hippocampus, cortex, and spinal cord starting at 3 months with age-dependent increases. Hyperphosphorylation, conformation changes, and mislocalization.
-
Neuronal Loss at 52
Neuron loss in the hippocampus and cortex at 12 months.
-
Gliosis at 43
Astrocytosis and microgliosis at 10 months.
-
Synaptic Loss at 87
Synaptophysin, but not PSD95, decreased in hippocampus and cortex at 12 months. By Golgi staining, spines unchanged in CA1 at 10 months, increased in CA3 at 12 months, and decreased in CA1 and CA3 at 16 months.
-
Cognitive Impairment at 70
No change at 10 months but at 16 months deficits in learning and memory (Morris water maze).
Absent
-
Changes in LTP/LTD at
Unchanged at 12 months.
No Data
-
Plaques at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT A152T | MAPT: Knock-In | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses. |
Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal. |
hTau.P301S
Observed
-
Tangles at 17
Neurofibrillary tangles detected as early as 4 months of age.
-
Neuronal Loss at 13
Neuronal loss starting at 3 months. Loss is especially prominent in the spinal cord with notable loss of superficial cortical neurons as well (Hampton et al., 2010).
-
Gliosis at 22
Astrocytosis, as measured by GFAP reactivity, in 6 month-old animals. Microglial activation in the brain stem and spinal cord of 5 month-old animals by OX42 staining (Bellucci et al., 2004).
-
Cognitive Impairment at 11
Memory deficit starting at 2.5 months as assessed by the Morris water maze (Xu et al., 2014), but no deficit at 2 months (Scattoni et al., 2010).
Absent
-
Plaques at
Absent.
No Data
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT P301S | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis. |
Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months. |
hTREM2-KI
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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: Knock-In | Alzheimer's Disease |
hTREM2-R47H_KI
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 R47H | TREM2: Knock-In | Alzheimer's Disease |
Il1rap KO/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, Il1rap, Trem2 | TREM2 R47H | APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
J20 (PDGF-APPSw,Ind)
Observed
-
Plaques at 22
At 5-7 months of age diffuse amyloid-β plaques deposit in the dentate gyrus and neocortex. Amyloid deposition is progressive with widespread plaques by 8-10 months. Aβ puncta are deposited in the hippocampus as early as 1 month (Hong et al., 2016).
-
Neuronal Loss at 12
Cell loss varies by brain region. No significant neuronal loss was observed in the CA3 region of the hippocampus at 6, 12, 24 and 36 weeks of age nor in the CA1 region at 6 weeks; however, at 12, 24, and 36 weeks significant neuronal loss was observed in the CA1 region compared to age-matched wild-type animals (Wright et al., 2013).
-
Gliosis at 24
At 24 and 36 weeks a significant increase in the number of reactive GFAP+ astrocytes and CD68+ microglia was observed in the hippocampi of J20 mice compared to age-matched wild-type controls. No significant difference was observed at 6 and 12 weeks (Wright et al., 2013).
-
Synaptic Loss at 15
Age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and homer immunoreactivity in the hippocampus by 3 months; synapse loss was confirmed by electron microscopy. No significant difference was seen at 1 month (Hong et al., 2016).
-
Changes in LTP/LTD at 13
Basal synaptic transmission is impaired between 3-6 months; extracellularly recorded field EPSPs at the Schaffer collateral to CA1 synapse in acute hippocampal slices were on average smaller in amplitude than those seen in wild-type mice. Significant deficits in LTP at the Schaffer collateral–CA1 synapse compared with control mice at 3-6 months (Saganich et al., 2006).
-
Cognitive Impairment at 16
Deficits in spatial memory and learning appear as the mice age. By 4 months, J20 mice demonstrate spatial reference memory deficits as measured by the radial arm maze (Wright et al., 2013) and Morris water maze (Cheng et al., 2007).
Absent
-
Tangles at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | APP: Transgenic | Alzheimer's Disease | Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity. |
Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated. |
JNPL3(P301L)
Observed
-
Tangles at 20
Neurofibrillary tangles develop in an age and gene-dose dependent manner; as early as 4.5 months in homozygotes and 6.5 months in heterozygotes. Tangles and Pick-body-like neuronal inclusions in the amygdala, septal nuclei, preoptic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord (Lewis et al., 2000).
-
Neuronal Loss at 43
Neuronal loss, especially in the spinal cord, most prominent in the anterior horn (Lewis et al., 2000).
-
Gliosis at 43
Astrogliosis (as measured by GFAP reactivity) in brainstem, diencephalon, and basal telencephalon by 10 months (Lewis et al., 2000).
Absent
-
Plaques at
Absent.
No Data
-
Cognitive Impairment at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT P301L | MAPT: Transgenic | Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease | Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord. |
By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization. |
Kif21b*T82T/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Kif21b, APOE, Trem2 | TREM2 R47H | Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
MAPT(H1.0)-GR
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
MAPT, MAPT-AS1, Mapt | MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Unknown. |
Unknown. |
MAPT(H2.1)-GR
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
MAPT, MAPT-AS1, Mapt | MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Unknown. |
Unknown. |
MAPT knock-in
Observed
Absent
-
Plaques at
No amyloid plaques at 24 months of age.
-
Tangles at
No neurofibrillary tangles at 24 months of age.
-
Neuronal Loss at
Neurodegeneration not apparent up to 2 years of age.
-
Gliosis at
No astrogliosis or microgliosis observed at 24 months.
-
Cognitive Impairment at
At 12 months of age, MAPT knock-in mice perform similarly to wild-type mice in the Y-maze test of working memory (only males tested).
No Data
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT: Knock-In | Alzheimer's Disease, Other Tauopathy | No evidence of increased neuroinflammation, neuronal death, or brain atrophy in MAPT knock-in mice, compared with wild-type mice. |
MAPT knock-in mice perform similarly to wild-type mice in the Y-maze test of working memory. |
McGill-R-Thy1-APP
Observed
-
Plaques at 24
Amyloid plaques present in homozygotes, appearing in hippocampus at 6 months and cortex at 13 months. Plaques are generally absent in hemizygotes.
-
Neuronal Loss at 72
A 22 percent reduction in the number of neurons was seen in the subiculum of homozygous transgenic rats at 18 months.
-
Gliosis at 24
Microgliosis and astrogliosis observed in homozyogotes.
-
Synaptic Loss at 80
Reduction in cholinergic synaptic boutons seen at 20 months in homozygous transgenic rats.
-
Changes in LTP/LTD at 14
Impairments in long-term potentiation in CA1 by 3.5 months of age.
-
Cognitive Impairment at 12
Deficits in Morris water maze and fear conditioning test are apparent by 3 months of age in both hemizygous and homozygous transgenic rats.
Absent
No Data
-
Tangles at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | APP: Transgenic | Alzheimer's Disease | Hemizygotes: intraneuronal Aβ in hippocampus and cortex by one week, but no plaques even at advanced ages. Homozygotes: intraneuronal Aβ in hippocampus and cortex by one week; amyloid plaques in hippocampus beginning at 6 months, in cortex beginning at 13 months. |
Cognitive deficits are apparent by three months of age in both hemizygous and homozygous transgenic rats. |
Mthfr*C677T/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Mthfr, APOE, Trem2 | TREM2 R47H | Mthfr: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
mThy-1 3R Tau (line 13)
Observed
-
Tangles at 34
Pick-body like inclusions of aggregated tau appeared in the hippocampus and cortex by 8-10 months. Inclusions were positive for Bielchowsky silver stain but negative for Gallyas-silver stain and Thioflavin-S.
-
Neuronal Loss at 34
Neuronal loss occurred by 8-10 months as evidenced by decreased NeuN staining in the dentate gyrus and CA3 regions of the hippocampus. Neocortical volume also decreased.
-
Gliosis at 35
Astrogliosis was seen by 8-10 months in the neocortex and hippocampus. Some GFAP+ astrocytes also contained 3R tau.
-
Cognitive Impairment at 26
By 6-8 months memory impairment was evident as a failure to habituate to a novel environment. This deficit was not present at 3-4 months. At 8-10 months, transgenics also took longer than wild-type mice to find the hidden platform in the Morris water maze.
Absent
-
Plaques at
Absent.
No Data
-
Synaptic Loss at
Synapto-dendritic damage manifested as reduced dendritic density, reduced MAP2 immunoreactivity, and accumulation of 3R tau in dendrites.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT L266V, MAPT G272V | MAPT: Transgenic | Frontotemporal Dementia, Pick's disease, Alzheimer's Disease | Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology. |
Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test. |
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. |
NSE-APP751
Observed
-
Plaques at 8
Aβ deposits were observed as early as two months of age. These deposits were diffuse and extracellular and had a “cotton-like” appearance. Classic mature plaques were not observed.
-
Gliosis at 95
Gliosis was noted in a single 22-month-old animal with extensive Aβ deposits (Higgins et al., 1994).
-
Cognitive Impairment at 52
Deficits in spatial memory and learning appear as the mice age. At 12 months the mice demonstrate learning and memory deficits as measured by a water-maze task and in spontaneous alternation in a Y maze (Moran et al., 1995). At six months cognition is largely normal.
Absent
-
Tangles at
Classic tangles were not observed, but aberrant tau immunoreactivity was observed as early as two months.
-
Neuronal Loss at
Cell death was not formally assessed, however, overt neuronal death was not seen.
No Data
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP: Transgenic | Alzheimer's Disease | Age-dependent increase in Aβ deposits and tau immunoreactivity. |
Learning and memory deficits are age-dependent as assessed on spontaneous alternation in a Y maze and in the water-maze task. |
PA-Rab5
Observed
-
Neuronal Loss at 28
Loss of basal forebrain cholinergic neurons, beginning at 7 months.
-
Synaptic Loss at 34
Loss of spines in CA3 and dentate gyrus regions of the hippocampus, observed in 8.5-month-old mice.
-
Changes in LTP/LTD at 24
Pronounced defect in LTD and slight impairment in LTD at Schaffer collateral-CA1 synapses in hippocampal slices from 6-month-old mice.
-
Cognitive Impairment at 24
When tested at 6 months of age, the performance of PA-Rab5 mice differed from wild-type controls in a novel object recognition test.
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Gliosis at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
RAB5A | RAB5A: Transgenic | Alzheimer's Disease | Enlarged Rab5-positive endosomes, tau hyperphosphorylation, synapse loss in hippocampus, and loss of basal forebrain cholinergic neurons. |
When tested at 6 months of age, the performance of PA-Rab5 mice differed from wild-type controls in a novel object recognition test. |
PDAPP(line109)
Observed
-
Plaques at 26
In heterozygous mice no plaque pathology at 4-6 months. At 6-9 months mice begin to exhibit deposits of human Aβ in the hippocampus, corpus callosum, and cerebral cortex. Plaques become more extensive with age and vary in size and structure including diffuse irregular plaques and compact cored plaques (Games et al., 1995).
-
Gliosis at 26
GFAP-positive astrocytes and activated microglia associated with plaques (Games et al., 1995).
-
Synaptic Loss at 35
Decreased synaptic density in the dentate gyrus as measured by synaptophysin immunoreactivity. Also decreased dendritic density as measured by MAP2 immunoreactivity (Games et al., 1995).
-
Changes in LTP/LTD at 17
Alterations in LTP induced by theta burst stimulation at 4-5 months which is prior to plaque formation; although the potentiation immediately after TBS was comparable to control mice, the potentiation decayed more rapidly in PDAPP mice. Also paired pulse facilitation was enhanced. Responses to high frequency stimulation bursts were distorted (Larson et al., 1999).
-
Cognitive Impairment at 13
Deficits in a variety of memory paradigms from a young age. Robust deficits in the radial arm maze at 3 months (deficits appear before amyloid plaque deposits). Object recognition, 6, 9-10 months. Operant learning, 3, 6 months (Dodart et al., 1999).
Absent
-
Tangles at
No paired helical filaments or aggregates, but phosphorylated tau immunoreactivity is observed in dystrophic neurites after 14 months (Masliah et al., 2001).
-
Neuronal Loss at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP V717F (Indiana) | APP: Transgenic | Alzheimer's Disease | Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus. |
Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months. |
PDGF-APP(WT) (line I5)
Observed
-
Synaptic Loss at 9
By 2-4 months of age, there is a decrease in synaptophysin-immunoreactive presynaptic terminals compared to nonTg controls. Synaptophysin immunoreactivity decreases further with age.
Absent
-
Tangles at
Not observed.
-
Neuronal Loss at
Not observed.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP: Transgenic | Alzheimer's Disease | Expression of human APP in the brain especially in the neocortex and hippocampus. No plaques up to 24 months. |
Unknown. |
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. |
PLB4 (hBACE1)
Observed
-
Gliosis at 52
Increased GFAP-positive astrocytes at 12 months of age in the dentate gyrus, CA1 region of the hippocampus, and the piriform cortex. Gliosis is suspected to begin earlier than 12 months.
-
Cognitive Impairment at 13
Impaired spatial representation in a habituation task by 3 months of age. By 6 months, impaired learning and memory by a variety of tasks including the Y-maze, Morris water maze, and a test of the social transmission of food preference. These effects appear to be distinct from reduced motor activity and reduced anxiety.
Absent
-
Plaques at
Plaques virtually absent, minimal small sparse plaques. However, prominent extracellular Aβ staining surrounding neuronal cell bodies, including Aβ multimers (e.g. Aβ*56 and Aβ hexamers).
-
Tangles at
Preliminary analysis did not find abnormal phosphorylation or conformational changes in tau.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
BACE1 | BACE1: Transgenic | Alzheimer's Disease | Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology. |
Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety. |
Plcγ2-P522R knock-in
Observed
-
Gliosis at 24
Astrogliosis revealed by GFAP immunohistochemistry in 6-month-old males. Microglial activation revealed by TSPO PET imaging in year-old females.
Absent
No Data
-
Plaques at
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 |
---|---|---|---|---|---|
Plcg2 | Plcg2: Knock-In | Alzheimer's Disease, Dementia with Lewy Bodies, Frontotemporal Dementia | Hypertrophic astrocytes in the hippocampi, revealed by GFAP immunohistochemistry. Microglial activation revealed by TSPO PET imaging. |
Unknown. |
Plcg2 KO
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Plcg2 | Plcg2: Knock-Out | Alzheimer's Disease | Unknown. |
Unknown. |
Plcg2*M28L/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
APOE, Plcg2, Trem2 | TREM2 R47H | APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
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
Observed
-
Gliosis at 24
Plcg2*P522R knock-in mice had a slightly higher density of Iba1-positive microglia than wild-type mice. Microglia in the knock-in animals were simpler in shape—with less ramified processes—and contained a greater density of puncta immunoreactive for the lysosomal marker CD68, compared with wild-type microglia.
Absent
-
Synaptic Loss at
Synapse number in hippocampal CA1—assessed as the density of puncta immunoreactive for the presynaptic marker bassoon or the postsynaptic marker PSD95—did not differ between Plcg2*P522R and wild-type mice. However, a slight decrease in the number of thin spines was observed in mutation carriers, while numbers of stubby and mushroom spines did not differ between the genotypes.
No Data
-
Plaques at
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 |
---|---|---|---|---|---|
Plcg2 | Plcg2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
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. |
Plcg2*P522R x APP NL-G-F
Observed
-
Plaques at 24
ThioflavinS-positive amyloid plaques observed in mice studied at 6 months of age. Higher plaque burdens than APPNL-G-F.
-
Gliosis at 24
Microgliosis observed in mice studied at 6 months of age. Attenuated microglia-plaque interactions in the hippocampus, compared with APPNL-G-F.
Absent
-
Synaptic Loss at
The P522R variant attenuated the synapse loss observed in APPNL-G-F mice with wild-type PLCγ2.
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 |
---|---|---|---|---|---|
Plcg2, App | APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic) | Plcg2: Knock-In; App: Knock-In | Alzheimer's Disease | Sex- and region-dependent increases in plaque burden, and decreases in microglia-plaque interactions, in Plcg2*P552R x APPNL-G-F mice, compared with APPNL-G-F. |
Unknown. |
PS19 with humanized TREM2 (common variant)
Observed
-
Tangles at 37
Tangles revealed using antibody PG5 at 9 months.
-
Neuronal Loss at 38
At 9 months, atrophy of hippocampus and entorhinal/piriform cortex and pronounced ventricular expansion. Thinning of the granule cell layer of the dentate gyrus and pyramidal cell layer of the piriform cortex, compared with PS19 mice carrying TREM2-R47H.
-
Gliosis at 39
Elevated expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the R47H variant of TREM2.
-
Synaptic Loss at 40
Fewer synapses and more dystrophic synapses, compared with PS19 mice carrying the R47H variant of TREM2.
Absent
No Data
-
Plaques at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT, TREM2, Trem2 | MAPT P301S | MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out | Alzheimer's Disease, Frontotemporal Dementia | Brain atrophy by 9 months of age. Increased microgliosis, astrogliosis and synapse loss, compared with PS19 mice carrying TREM2 with the R47H mutation. |
Not known. |
PS19 with humanized TREM2 (R47H)
Observed
-
Tangles at 36
Tangles revealed using antibody PG5 at 9 months.
Absent
No Data
-
Plaques at
No data.
-
Neuronal Loss at
No data relative to wild-type mice, but at 9 months of age, the volumes of the hippocampus and entorhinal/piriform cortex are larger, and the granule cell layer of the dentate gyrus and pyramidal cell layer of the piriform cortex are thicker, in PS19-TREM2R47H mice, compared with PS19 mice carrying the common variant of human TREM2.
-
Gliosis at
At 9 months of age, decreased expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the common variant of TREM2, but no data relative to wild-type mice.
-
Synaptic Loss at
At 9 months of age, more synapses and fewer dystrophic synapses, compared with PS19 mice carrying the common variant of TREM2, but no data relative to wild-type mice.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT, TREM2, Trem2 | MAPT P301S, TREM2 R47H | MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out | Alzheimer's Disease, Frontotemporal Dementia | Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2. |
Not known. |
PS1 conditional Knock-out
Observed
-
Cognitive Impairment at 22
Mild impairment of spatial learning and memory in the Morris water maze observed in 5 month-old mice (Yu et al., 2001).
Absent
-
Plaques at
Absent.
-
Tangles at
Absent.
-
Neuronal Loss at
Absent.
-
Changes in LTP/LTD at
Mice at 3-6 months of age exhibit normal paired-pulse facilitation, LTP, and LTD in the Schaffer collateral pathway of the hippocampus (Yu et al., 2001).
No Data
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
PSEN1 | PSEN1: Conditional Knock-out | Alzheimer's Disease | Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments. |
Subtle but significant deficits in long-term spatial memory in the Morris water maze. |
PS2APP
Observed
-
Plaques at 26
Age-associated development of plaques: none at 3 months, overt Aβ deposition at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months (Ozmen et al., 2009; Weidensteiner et al. 2009).
-
Gliosis at 26
Gliosis at 6 months (personal communication, Laurence Ozmen).
-
Changes in LTP/LTD at 43
A strong increase in LTP and post-tetanic potentiation induced by tetanic stimulation in hippocampal slices of 10 month-old animals compared to wild-type mice (Poirier et al., 2010).
-
Cognitive Impairment at 35
Cognitive impairment is detected by the Morris water maze (probe trial 2) at 8 and 12 months of age, not at 3 months (personal communication Laurence Ozmen).
Absent
-
Tangles at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months. |
Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months. |
PS2APP (PS2(N141I) x APPswe)
Observed
-
Plaques at 39
Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution over time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei (Richards et al., 2003).
-
Gliosis at 39
An inflammatory response indicated by the presence of activated microglia and astrocytes begins around 9 months. The onset, distribution, and abundance of activated microglia and astrocytes correlate with Aβ deposition.
-
Cognitive Impairment at 35
Age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze (Richards et al., 2003).
Absent
-
Tangles at
Absent.
-
Changes in LTP/LTD at
No difference in LTP in the dentate gyrus at 3 and 10 months compared to wild-type mice (Richards et al., 2003).
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN2 | APP K670_M671delinsNL (Swedish), PSEN2 N141I | APP: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition. |
Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze. |
PS/APP
Observed
-
Plaques at 26
Large amounts of Aβ accumulate in the cerebral cortex and hippocampus, starting around 6 months and increasing with age. Other brain regions are affected later. Both diffuse and fibrillar plaques form (Gordon et al., 2002).
-
Neuronal Loss at 79
Neuronal loss in the CA1 region of the hippocampus has been reported at 22 months accompanied by reduced glucose utilization (Sadowski et al., 2004).
-
Gliosis at 26
GFAP-positive astrocytes appear first in the cortex in the vicinity of the developing Aβ deposits. Numbers increase with age, becoming confluent. Numbers of resting microglia (positive for complement receptor-3) increase in the vicinity of deposits at 6 months, but activated microglia (positive for MHC-II) are negligible before 12 months and more variable (Gordon et al., 2002).
-
Cognitive Impairment at 12
Double and single transgenic mice had reduced spontaneous alternation performance in a “Y” maze, a test of spatial memory, at 12-14 weeks, before substantial Aβ deposition (Holcomb et al., 1998). Progressive age-related cognitive impairment is seen later in select tasks (e.g. water maze acquisition and radial arm water maze working memory)(Arendash et al., 2001).
Absent
-
Tangles at
Neurofibrillary tangles are not associated with this model, but hyperphosphorylated tau is detected, starting at 24 weeks, appearing as punctate deposits near amyloid deposits in the cortex and hippocampus (Kurt et al., 2003).
No Data
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C) | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter, cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation. |
Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels. |
PS cDKO
Observed
-
Neuronal Loss at 9
Significant increase (about 8-fold) in apoptotic neurons at 2 months of age, although the total number of cortical neurons is not significantly altered due to the low basal level of apoptosis in the cerebral cortex. By 4 months of age, the cumulative loss of cortical neurons reaches about 9 percent of all cortical neurons.
-
Gliosis at 17
Astrogliosis and microgliosis; up-regulation of GFAP and other inflammatory markers are observed in the neocortex and hippocampus at 6 months, and this increases with age (Wines-Samuelson et al., 2010, Beglopoulos et al., 2004).
-
Synaptic Loss at 26
Reduction in synaptophysin immunoreactivity in hippocampal CA1 pyramidal neurons by 6 months. Reduction in dendritic spines by 9 months (Saura et al., 2004).
-
Cognitive Impairment at 9
Deficits in the Morris water maze and contextual fear conditioning are mild at 2 months, but become more severe with age (Saura et al., 2004).
Absent
-
Plaques at
Absent.
-
Tangles at
Tangles are absent, but hyperphosphorylation of tau has been reported in 9 month-old mice.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
PSEN1, PSEN2 | PSEN1: Conditional Knock-out; PSEN2: Knock-Out | Alzheimer's Disease | At 2 months the number of apoptotic neurons is elevated about 8-fold. By 6 months, about 18 percent of of cortical neurons are lost. Up-regulation of inflammatory markers and progressive astrogliosis and microgliosis in the neocortex and hippocampus. |
Impairments in hippocampal learning and memory as indicated by Morris water maze and contextual fear conditioning evident by 2 months and worsens with age. |
Psen1 L435F knock-in
Observed
Absent
-
Plaques at
No plaques at 15 days of age.
-
Neuronal Loss at
No neuron loss at 15 days of age.
-
Gliosis at
No astrogliosis or microgliosis at 15 days of age.
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 |
---|---|---|---|---|---|
Psen1, App | PSEN1 L435F | Psen1: Knock-In; App: Knock-In | Alzheimer's Disease | None observed in 15-day-old rats. |
Unknown. |
PWK.APP/PS1
Observed
-
Plaques at 32
Thioflavin S-positive amyloid plaques are present in the cortex and CA1 region of the hippocampus by 8 months of age, with females having more plaques in the cortex than males.
-
Gliosis at 33
Plaque-associated microgliosis observed by 8 months.
Absent
-
Tangles at
Not observed.
-
Neuronal Loss at
Not observed.
-
Cognitive Impairment at
Working memory and short-term memory were intact at 7 to 8 months, as assessed by tests in the Y-maze.
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), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques and plaque-associated gliosis by 8 months. |
Transgenic mice are hyperactive and aggressive. Working memory and short-term memory are intact at 7 to 8 months, as assessed by tests in the Y-maze. |
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. |
rTgTauEC
Observed
-
Tangles at 78
By 18 months of age, Gallyas silver-positive staining is observed, indicative of paired helical filaments. This is followed by thioflavin-S staining at 24 months. Tau pathology develops first in neurons of the medial EC expressing human tau, followed by neurons in the dentate gyrus, CA1 and CA2/3(de Calignon et al., 2012).
-
Neuronal Loss at 83
Neuronal loss is detectable by 24 months of age in areas with transgene expression (e.g. layer II of the EC and parasubiculum), compared with age-matched mice expressing only tTA. Significant neuronal loss was not observed at 21 months (de Calignon et al., 2012).
-
Gliosis at 104
Microglial activation and astrogliosis by 24 months of age, in conjunction with axonal degeneration and neuronal loss (de Calignon et al., 2012).
-
Synaptic Loss at 104
By 24 months of age pre- and post-synaptic densities were reduced in the middle third of the molecular layer of the dentate gyrus as measured by synapsin-1 and PSD-95 staining (de Calignon et al., 2012).
-
Changes in LTP/LTD at 70
At 16 months of age, subtle differences in electrophysiological properties have been observed in the perforant pathway, including a decrease in LTP and an increase in the probability of neurotransmitter release (Polydoro et al., 2014).
-
Cognitive Impairment at 70
Very mild and specific deficits in contextual fear conditioning at 16 months of age, but no deficits in the radial arm maze (Polydoro et al., 2014).
Absent
-
Plaques at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT P301L | MAPT: Transgenic | Frontotemporal Dementia, Alzheimer's Disease | Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss. |
Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test. |
rTg(tauP301L)4510
Observed
-
Tangles at 17
Pretangles as early as 2.5 months. Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months.
-
Neuronal Loss at 24
Decreased (~60%) CA1 hippocampal neurons by 5.5 months with significant loss in brain weight. Progressive loss of neurons and brain weight in 7 and 8.5 month mice with ~23% of CA1 pyramidal cells remaining at 8.5 months. Gross atrophy of the forebrain by 10 months.
-
Synaptic Loss at 35
Significant loss of dendritic spines at 8-9 months (~30% decrease in spine density in somatosensory cortex).
-
Cognitive Impairment at 11
Retention of spatial memory (Morris Water Maze) became impaired from 2.5 to 4 months. No significant motor impairments up to 6 months. Spatial memory improved when transgene suppressed by dox.
Absent
-
Plaques at
Absent.
No Data
-
Changes in LTP/LTD at
LTP at the Schaffer collateral-CA1 synapse is normal at 1.3 months, but impaired at 4.5 months.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT P301L | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia | Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60 percent) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (six to eight week) suppression of transgenic tau. |
Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved. |
SHR24
Observed
-
Tangles at 38
Argyrophilic neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem.
-
Synaptic Loss at 60
Decreased levels of synaptophysin and a decreased number of synaptic vesicles per synapse in animals at the end of the lifespan of this line.
Absent
-
Neuronal Loss at
No neuron loss was observed in the hippocampi or cortices of male rats examined at 15 month of age.
No Data
-
Plaques at
No data.
-
Gliosis at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
Sensorimotor deficits and abnormal reflexes observed as early as 3.5 months, but no data available from cognitive tests.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT: Transgenic | Alzheimer's Disease | Neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem, beginning at 9 to 10 months. No neuron loss was observed in the hippocampus or cortex. |
SHR24 rats exhibit age-dependent impairments in several neurobehavioral tests; hind-limb clasping during the tail-hang test is one of the earliest abnormalities to appear, evident by 3.5 months of age. |
SHR318
Observed
-
Tangles at 38
Argyrophilic neurofibrillary tangles are particularly prominent in the brainstem and spinal cord.
-
Cognitive Impairment at 18
At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze.
Absent
-
Neuronal Loss at
Neuron numbers in the hippocampi and brainstem gigantocellular reticular nucleus do not differ between 10.5-month SHR318 rats and non-transgenic rats.
No Data
-
Plaques at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT: Transgenic | Alzheimer's Disease | Neurofibrillary tangles first appear at 9 months and are particularly prominent in the brainstem and spinal cord. Axonal degeneration is observed in the brainstem and spinal cord of 10- to 12-month animals. |
At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze. Reflexes and sensorimotor coordination are impaired at 7 months. |
SHR72
Observed
-
Tangles at 30
Neurofibrillary tangles, demonstrated by Gallyas silver stain, are present in the brainstem and spinal cord.
-
Gliosis at 29
Astrogliosis and microgliosis are present in brainstem regions bearing neurofibrillary tangles.
Absent
-
Neuronal Loss at
Although neuron loss has not been documented, chromatolytic neurons and damaged axons were seen in the brains of 7-month animals, particularly in the brainstem reticular formation.
No Data
-
Plaques at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
Sensorimotor deficits and abnormal reflexes observed as early as 3 months, but no data available from cognitive tests.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
MAPT | MAPT: Transgenic | Alzheimer's Disease | Neurofibrillary tangles, demonstrated by Gallyas silver stain, were found the brainstems and spinal cords of terminal stage (7- to 8-month old) animals. Chromatolytic neurons and damaged axons were also observed at this stage. |
Sensorimotor deficits and loss of muscle strength are apparent at 3 months. This stage lasted about three months, and then rats experienced a rapid, dramatic decline in neurological function, succumbing within several days. |
SHRSP/FAD
Observed
-
Plaques at 69
Diffuse amyloid plaques observed at 16-18 months, the only age examined to date.
-
Tangles at 70
Occasional neurons appear to contain globose neurofibrillary tangles, as revealed by immunostaining using an antibody directed against tau phosphorylated at serine 422, an epitope found in paired helical filaments.
-
Gliosis at 71
Hypertrophied microglia and elevated levels of GFAP observed at 16-18 months, the only age examined to date.
-
Cognitive Impairment at 72
Working memory deficits as assessed by novel object recognition, but not as assessed by spontaneous alternation in the Y-maze, at 16-18 months, the only age examined to date.
Absent
-
Synaptic Loss at
Levels of SNAP25, synaptophysin, and drebrin do not differ from non-hypertensive, non-transgenic rats at 16-18 months, the only age examined to date.
No Data
-
Neuronal Loss at
A reduction in calbindin staining might reflect a loss of inhibitory neurons. Levels of caspase-cleaved actin, a marker of apoptosis, are elevated, compared with non-hypertensive, non-transgenic rats.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1: deltaE9 | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease, Vascular Dementia | Amyloid plaques, microgliosis, and possible astrogliosis. Occasional neurons appear to contain paired helical filament tau. Demyelination. Reduced calbindin immunoreactivity and increased levels of caspase-cleaved actin may indicate neuron loss. |
Hyperactive. Working memory deficits as assessed by novel object recognition, but not as assessed by spontaneous alternation in the Y-maze. |
Snx1*D465N/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss 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 |
---|---|---|---|---|---|
Snx1, APOE, Trem2 | TREM2 R47H | Snx1: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
Sorl1*A528T
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis 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 |
---|---|---|---|---|---|
Sorl1 | SORL1 A528T (SNP 13) | Sorl1: Knock-In | Alzheimer's Disease |
Sorl1*A528T/APOE4/Trem2*R47H
Observed
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic 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 |
---|---|---|---|---|---|
Sorl1, APOE, Trem2 | TREM2 R47H, SORL1 A528T (SNP 13), APOE C130R (ApoE4) | Sorl1: Knock-In; APOE: Knock-In; Trem2: Knock-In | Alzheimer's Disease | Unknown. |
Unknown. |
SORL1 transgenic (Cre-inducible)
Observed
Absent
-
Changes in LTP/LTD at
LTP at Schaffer collateral-CA synapses was similar in hippocampal slices from 3-month-old Rosa26Tg/+ and wild-type mice. The application of Aβ oligomers impaired LTP in slices from wild-type mice but did not affect LTP in SORL1 transgenic mice.
-
Cognitive Impairment at
Three-month-old Rosa26Tg/+ SORL1 transgenic mice performed similarly to wild-type mice in the acquisition and retention phases of the Morris Water Maze test. Hippocampal injection of Aβ oligomers prevented wild-type mice from learning the location of the escape platform but did not affect the performance of the transgenic mice.
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
SORL1 | SORL1: Transgenic | Alzheimer's Disease | Unknown. |
Normal performance in the Morris Water Maze. |
SORLA-deficient
Observed
Absent
-
Plaques at
No amyloid plaques observed up to 10 months of age. When SORLA-deficient mice are crossed with APP transgenic models of amyloidosis, amyloid deposition is accelerated, compared with the parental APP transgenic line.
No Data
-
Tangles at
No data.
-
Neuronal Loss at
Neuron loss was not seen in the substantia nigra and ventral tegmental areas, assessed at 5 weeks and 45 weeks. Data on neuron numbers are not available from other brain regions. Nigrostriatal connectivity appears to be disrupted in SORLA-deficient mice.
-
Gliosis at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No differences in LTP were observed in hippocampal slices from 10- to 12-month-old Sorl1-/- mice and slices from littermates heterozygous for the Sorl1 deletion (Rohe et al., 2008). It is not known whether LTP in these genotypes differs from that of wild-type mice.
-
Cognitive Impairment at
Compared with wild-type mice, SORLA-deficient mice exhibited more arm entries and more time spent in the open arms of the elevated plus maze—behaviors interpreted as evidence of hyperactivity and reduced anxiety. Hyperactivity was also noticed in the open field test.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
Sorl1 | Sorl1: Knock-Out | Alzheimer's Disease | Mice do not generate amyloid plaques. Disrupted nigrostriatal connectivity and thinner inner nuclear layer of the retina. |
Hyperactivity and reduced anxiety, compared with wild-type mice. |
TAS10 (thy1-APPswe)
Observed
-
Plaques at 52
Fibrillar amyloid plaques develop by 12 months in the cortex and hippocampus.
-
Gliosis at 26
Astrogliosis and microgliosis underway by 6 months of age in the dentate gyrus.
-
Synaptic Loss at 104
TAS10 mice initially have more synapses than non-Tg mice; specifically, greater numbers of synapses per neuron were documented at 12 and 18 months of age. However, by 24 months of age, TAS10 mice have fewer synapses than non-Tg mice.
-
Cognitive Impairment at 26
Deficits in spatial learning present by 6 months of age as measured by the Morris water maze. No difference from non-Tg at 2 months of age. Deficits in Y maze at 12 months. No deficit in fear conditioning up to 24 months of age.
Absent
-
Tangles at
Absent.
-
Neuronal Loss at
Qualitative difference in neuronal numbers at 24 months in specific regions of the hippocampus, but no significant neuronal loss.
-
Changes in LTP/LTD at
At 12 to 14 months of age, deficits in basal synaptic transmission have been observed in the CA1 region, but short- and long-term synaptic plasticity are relatively normal (Brown et al., 2005).
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP | APP K670_M671delinsNL (Swedish) | APP: Transgenic | Alzheimer's Disease | Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes. |
Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning. |