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16 Models
16 Visualizations
AD-related Research Models
Phenotypes Examined
- Plaques
- Tangles
- Neuronal Loss
- Gliosis
- Synaptic Loss
- Changes in LTP/LTD
- Cognitive Impairment
When visualized, these phenotypes will distributed over a 18 month timeline demarcated at the following intervals: 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.
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. |
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. |
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. |
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. |
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. |
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. |
TauA152T-AAV
Observed
-
Neuronal Loss at 10
Neuron loss in cortex, seen at 3 months.
-
Gliosis at 11
Astrogliosis, but not microgliosis, seen at 3 months.
-
Cognitive Impairment at 12
Deficits in contextual and cued fear conditioning, seen at 3 months.
Absent
No Data
-
Plaques at
No data.
-
Tangles at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| MAPT | MAPT A152T | MAPT: Virus | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Neuron loss and astrogliosis were observed in the cortices of 3-month-old mice. |
Compared with GFP-AAV controls, TauA152T-AAV mice showed deficits in contextual and cued fear conditioning, increased hyperactivity, and decreased rearing in the open-field test, and spent more time in the open arms of the elevated plus maze. TauA152T-AAV mice also exhibited motor impairment on the Rotarod. |
Tau P301L
Observed
-
Tangles at 35
Hyperphosphorylation, conformational changes, and aggregation of tau resulting in tangle-like pathology by 8 months.
-
Gliosis at 30
Astrogliosis by 7 months.
-
Changes in LTP/LTD at 26
Deficit in LTP in CA1 region of the hippocampus at 6 months, but enhanced LTP in the dentate gyrus at a young age (8-10 weeks).
-
Cognitive Impairment at 22
Age-associated deficit in two cognitive tests that do not depend heavily on motor ability, the passive avoidance task (significant deficit starting at 5 months, but not 2 or 3 months of age) and a novel object recognition task (significant deficit at 9 months, but not at 2, 3, 5, or 7 months of age) (Maurin et al., 2014).
Absent
-
Plaques at
Absent.
No Data
-
Neuronal Loss at
Unknown.
-
Synaptic Loss at
Unknown at advanced age. Young mice (1-2 months) have a significantly higher spine maturation index than controls. At 4-6 months, the spine maturation index remains high in the hippocampus, but is reduced to control levels in the cortex. Note, these results were generated using the progeny of Tau P301L x transgenic Thy1-YFP (Kremer et al., 2011).
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| MAPT | MAPT P301L | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia | Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF. |
Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months. |
TauP301L-AAV
Observed
-
Tangles at 24
Argyrophilic, Thioflavin S-positive neurofibrillary tangles in cortex and hippocampus.
-
Gliosis at 12
Astrogliosis and microgliosis observed at 3 months.
-
Cognitive Impairment at 24
Deficits in cued and contextual fear conditioning observed at 6 months.
Absent
-
Neuronal Loss at
No cortical neuron loss at 6 months.
No Data
-
Plaques at
No data.
-
Synaptic Loss at
The accumulation of a PSD95 fragment suggests the possibility of synaptic abnormalities, although synaptic structure and function have not been assessed directly.
-
Changes in LTP/LTD at
No data.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| MAPT | MAPT P301L | MAPT: Virus | Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy | Neurofibrillary tangles and gliosis, but no cortical neuron loss, at 6 months of age. |
Hyperactivity in the open field, decreased time spent in the center of open field, more time spent in the open arms of the elevated plus maze, and deficits in cued and contextual fear conditioning at 6 months of age. |
Tau P301S (Line PS19)
Observed
-
Tangles at 23
Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem and spinal cord at six months with progressive accumulation (Yoshiyama et al., 2007).
-
Neuronal Loss at 39
Neuron loss in the hippocampus and entorhinal cortex by nine to12 months, as well as in the amygdala and neocortex becoming more severe by 12 months (Yoshiyama et al., 2007).
-
Gliosis at 11
Microgliosis at three months, especially in the white matter of the brain and spinal cord. Increased microgliosis by six months in white and gray matter of the hippocampus, amygdala, entorhinal cortex, and spinal cord. Microglial activation precedes astrogliosis (Yoshiyama et al., 2007).
-
Synaptic Loss at 13
Synaptophysin immunoreactivity decreased progressively from three to six months in the CA3 region of the hippocamus. Impaired synaptic function (Yoshiyama et al., 2007).
-
Changes in LTP/LTD at 26
Reduced LTP in the CA1 region of the hippocampus at six months. Altered basal synaptic transmission (smaller fiber volley amplitude, fEPSP slopes, and amplitudes) (Yoshiyama et al., 2007). Impaired hippocampal LTP as measured in freely moving mice (Lasagna-Reeves, 2016).
-
Cognitive Impairment at 27
Impairments in spatial learning and memory ability in the Morris water maze in six-month-old animals (Takeuchi et al., 2011). Impaired memory in assays of contextual fear conditioning (Lasagna-Reeves 2016).
Absent
-
Plaques at
Absent.
No Data
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| MAPT | MAPT P301S | MAPT: Transgenic | Alzheimer's Disease, Frontotemporal Dementia | Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis. |
Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months. |
TauPS2APP
Observed
-
Plaques at 17
Rare amyloid plaques at 4 months, plaques become more abundant with age. By 8 months the number of amyloid plaques increases considerably in the subiculum and the CA1 region of the hippocampus (Grueninger et al., 2010).
-
Tangles at 70
Abnormally phosphorylated tau is detectable at 4 months in both TauPS2APP and tau single transgenic mice especially in the subiculum, amygdala, and the CA1 region of the hippocampus. Tau pathology increases with age with numerous tangle-like deposits in the hippocampus confirmed by Gallyas silver staining at 16 months (Grueninger et al., 2010).
-
Cognitive Impairment at 17
Impairment is not age-associated and does not progress from age 4 months to 12 months (Grueninger et al., 2010).
Absent
-
Neuronal Loss at
No overt neuronal loss in the hippocampus at 16 months (Grueninger et al., 2010).
No Data
-
Gliosis at
Unknown.
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| APP, MAPT, PSEN2 | APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I | APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic | Alzheimer's Disease | Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss. |
Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology. |
Tg2576/Tau(P301L) (APPSwe-Tau)
Observed
-
Plaques at 39
Plaques develop gradually with age. No plaques at 5 months. Very few small plaques at 6 and 7 months. By 9 months plaques scattered throughout the cortex, hippocampus and amygdala, continue to increase at 12 months. Similar distribution as Tg2576.
-
Tangles at 13
Neurofibrillary tangles in the spinal cord and pons as early as 3 months, but more consistent and numerous by 6 months. Tangles morphologically similar to those in JNPL3 mice but older bigenic female mice had a marked increase in neurofibrillary tangles in limbic areas by 6 months, especially the olfactory cortex, entorhinal cortex and amygdala (Lewis et al., 2001).
-
Gliosis at 13
Reactive astrocytes and microglia as early as 3 months in the hippocampus as measured by GFAP and CD45. Increased astrocytosis with age especially in limbic areas with the most neurofibrillary tangles. Microglia especially concentrated around plaques at 9 and 12 months (Lewis et al., 2001).
Absent
No Data
-
Synaptic Loss at
Unknown.
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| APP, MAPT | APP K670_M671delinsNL (Swedish), MAPT P301L | APP; MAPT: Transgenic | Alzheimer's Disease | Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis. |
Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming. |
THY-Tau22
Observed
-
Tangles at 13
Heterozygous animals develop tau pathology starting at 3-6 months. Pathology becomes more severe and widespread with age. Neurofibrillary tangle-like inclusions occur (Gallyas and MC1+) along with rare ghost tangles and paired helical filament-like structures (Schindowski et al., 2006).
-
Neuronal Loss at 52
Loss of cells in the CA1 region of the hippocampus from 12 months as measured by DAPI staining and Nissl/cresyl-violet (Schindowski et al., 2006). Also, a significant reduction in the number of choline acetyltransferase (ChAT)-immunopositive cholinergic neurons in the medial septum has been reported (Belarbi et al., 2011).
-
Gliosis at 13
Age-dependent increase in the number of GFAP+ astrocytes in the hippocampus (hilus, CA1, CA3), cerebral cortex, corpus callosum (Schindowski et al., 2006).
-
Changes in LTP/LTD at 39
Altered paired pulse facilitation (PPF), a form of presynaptic short-term plasticity in 9-10 month old heterozygous animals: PPF increased at 10 ms. Also at this age, impaired maintenance of long term depression as compared with wild-type littermates (Van der Jeugd et al., 2011). Deficit in basal synaptic transmission in the hippocampus, but normal LTP (Schindowski et al., 2006).
-
Cognitive Impairment at 26
Non-spatial memory affected as early as 6 months; spatial memory impaired only after 9 months (Van der Jeugd et al., 2013). Impaired appetitive responding (Lo et al., 2013).
Absent
-
Plaques at
Absent.
No Data
| Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
|---|---|---|---|---|---|
| MAPT | MAPT G272V, MAPT P301S | MAPT: Transgenic | Frontotemporal Dementia, Alzheimer's Disease | A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis. |
Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity. |
Trem2 KO (Colonna) x PS19
Observed
-
Gliosis at 36
Microgliosis and astrogliosis by 9 months (the earliest age studied).
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 |
|---|---|---|---|---|---|
| Trem2, MAPT | MAPT P301S | Trem2: Knock-Out; MAPT: Transgenic | Frontotemporal Dementia, Alzheimer's Disease | Microgliosis, astrogliosis, and brain atrophy in Trem2-/-PS19 mice are greatly attenuated compared with Trem2+/+PS19 animals. |
No data. |