Research Models
Selected Results
12 Models
Name | Other Names | Strain Name | Genetic Background | Gene | Mutation | Modification Info | Modification | Disease | Neuropathology | Behavior/Cognition | Other Phenotype | Availability | Primary Paper | Visualization | |
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Mouse Models (10) |
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APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line | Inbred C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic) | A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter. | APP: Transgenic | Alzheimer's Disease, Cerebral Amyloid Angiopathy | Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. | At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. | Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus. | Cryopreserved. Contact Lennart Mucke | Cheng et al., 2004 | Yes | |||
PDGF-APPSw,Ind, PDGF-hAPP695,751,770V171F, KM670/671NL, hAPPJ20, hAPP, Mucke mice | B6.Cg-Zbtb20Tg(PDGFB-APPSwInd)20Lms/2Mmjax | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. | 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. | On the C57BL/6J background hippocampal hyperexcitability was observed and cortical and hippocampal spontaneous nonconvulsive seizures. | The Jackson Lab; available through the JAX MMRRC Stock# 034836-JAX; Live | Mucke et al., 2000 | Yes | ||
hAPP695Indiana, elan mouse, PDAPP, PD-APP | C57B6 x DBA2 | APP | APP V717F (Indiana) | A PDGF-driven human APP minigene with the V717F (Indiana) mutation. The construct contained APP introns 6-8 allowing alternative splicing of exons 7 and 8. | 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. | Alterations in sleep/wake states, thermoregulation, and motor activity. | Unknown | Games et al., 1995, Rockenstein et al., 1995 | Yes | |||
APP(Swedish,Indiana), line J9, hAPPJ9, hAPPlow | C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. | APP: Transgenic | Alzheimer's Disease | Amyloid plaques at 8-10 months, but not at 2-4 months when deficits in synaptic transmission are observed. Approximately 20% of mice had plaques at 5-7 months, 50% at 8-10 months, and 100% by 21-25 months. | Unknown. | Deficits in synaptic transmission at 2-4 months, prior to amyloid deposition. | Available through Lennart Mucke | Hsia et al., 1999 | No | |||
line 102 | B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax | C57BL/6 x C3HeJ; backcrossed to C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. | APP: Transgenic | Alzheimer's Disease | APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest doxycycline sensitivity relative to lines 107 and 885. | Hyperactivity. | The Jackson Lab; available through the JAX MMRRC Stock# 034845; Cryopreserved | Jankowsky et al., 2005 | No | |||
line 107 | B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax | C57BL/6 x C3HeJ; backcrossed to C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. | APP: Transgenic | Alzheimer's Disease | APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Intermediate expression of transgene and doxycycline sensitivity relative to lines 102 and 885. | Hyperactivity. | The Jackson Lab; available through the JAX MMRRC Stock# 034846; Cryopreserved | Jankowsky et al., 2005 | No | |||
line 885 | B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax | C57BL/6 x C3HeJ; backcrossed to C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. | APP: Transgenic | Alzheimer's Disease | APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest transgene expression and highest doxycycline requirement relative to lines 102 and 107. | Hyperactivity. | The Jackson Lab; available through the JAX MMRRC Stock# 034834; Cryopreserved | Jankowsky et al., 2005 | No | |||
APP(swe/ind) CRND8 | Hybrid C3H/He-C57BL/6 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Transgene contains human APP695 with the Swedish mutation (KM670/671/NL) and Indiana mutation (V717F) under the control of the hamster prion (PrP) gene promoter. The expression cassette includes about 90 nucleotides of the APP 5'-untranslated region adjacent to the start codon and 269 nucleotides of the 3′-untranslated region. | APP: Transgenic | Alzheimer's Disease | Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months . | Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests. | Cholinergic dysfunction: decrease in the number of cholinergic neurons in the nucleus basalis magnocellularis by 7 months as measured by ChAT immunoreactivity. Enhanced auditory startle response and modest reduction in prepulse inhibition. | Available through the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto | Chishti et al., 2001 | Yes | |||
mAPP/DN-RAGE, APP/DN-RAGE | C57BL/6 | APP, RAGE (AGER) | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mice expressing a form of transgenic RAGE comprising a truncated form of the receptor with intact extracellular and membrane-spanning portions, but a deleted cytosolic tail driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661--now extinct). | APP: Transgenic; RAGE (AGER): Transgenic | Alzheimer's Disease | Diminished neuropathology compared with mice expressing mutant APP alone at both 3–4 and 14–18 months of age. | Preservation of spatial learning and memory compared with Tg-mAPP/RAGE animals. | No abnormalities with respect to reproductive fitness, development, basic neurological functioning, or longevity. | Available through Shirley ShiDu Yan | Arancio et al., 2004 | No | |||
APP/RAGE | C57BL/6 | APP, RAGE (AGER) | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | Mice expressing human wild-type RAGE driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661-now extinct) | APP: Transgenic; RAGE (AGER): Transgenic | Alzheimer's Disease | Increased activation of microglia and astrocytes compared to mice expressing mutant APP alone. | Abnormalities in spatial learning and memory at 3-4 months of age, whereas deficits occur later in mice expressing mutant APP alone and are less severe. | Available through Shirley ShiDu Yan | Arancio et al., 2004 | No | ||||
Rat Models (2) |
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F344-Tg(APP)21Besey | Fischer 344 | APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | A lentiviral vector carrying a human APP695 transgene was injected into Fischer 344 zygotes. This transgene contains the Swedish and Indiana mutations and is driven by the ubiquitin-C promoter. | 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. | Available from the Rat Resource & Research Center, Stock# 00636; cryorecovery, sperm | Agca et al., 2008 | Yes | ||||
Fischer 344 | APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP V717F (Indiana), PSEN1 L166P | APP+PS1 transgenic rats express human APP with the Swedish and Indiana mutations and human PSEN1 with the L166P mutation. Both transgenes are driven by the ubiquitin-C promoter. | 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. | Agca et al., 2016, Klakotskaia et al., 2018 | Yes |
6 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+.
APP21
Observed
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Neuronal Loss at 76
Necrotic neurons in hippocampus and cortex of female rats.
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Gliosis at 64
Activated (MHCII-positive) microglia present in white matter tracts at 15 months.
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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
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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.
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Synaptic Loss at
No data.
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Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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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. |
APP+PS1
Observed
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Plaques at 76
Abundant plaques in hippocampus and subiculum, scattered plaques in cortex.
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Neuronal Loss at 76
Necrotic neurons in hippocampus and cortex.
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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 |
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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. |
Arc48 (APPSw/Ind/Arc)
Observed
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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).
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Gliosis at 13
Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).
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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 |
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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. |
J20 (PDGF-APPSw,Ind)
Observed
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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).
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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).
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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).
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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).
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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).
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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
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Tangles at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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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. |
PDAPP(line109)
Observed
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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).
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Gliosis at 26
GFAP-positive astrocytes and activated microglia associated with plaques (Games et al., 1995).
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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).
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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).
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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).
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Neuronal Loss at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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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. |
TgCRND8
Observed
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Plaques at 13
Amyloid deposition progresses with age. Thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques appear first in the subiculum, amygdala and frontal cortex, spread to the dentate gyrus, the olfactory bulb, and later thalamus, cerebral vasculature, and striatum, followed by the cerebellum and brain stem (Chishti et al., 2001).
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Neuronal Loss at 26
Variable cell loss by region. No difference in overall cell count, but fewer hippocampal neurons at 6 months (Brautigam et al., 2012).
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Gliosis at 13
Microglia activation appears simultaneously with Aβ deposition, with only rare activated microglia at 9-10 weeks, but by 13-14 weeks microglia cluster around Aβ deposits in the cerebral cortex and hippocampus; numerous by 20 weeks. Robust astrogliosis slightly later with clusters of GFAP+ astrocytes emerging around plaques at 13-14 weeks (Dudal et al., 2004).
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Synaptic Loss at 26
Reduced synaptophysin immunoreactivity in the vicinity of plaques at 6 months (Adalbert et al., 2009).
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Changes in LTP/LTD at 26
In hippocampal slices from 6- to 12-month-old mice basal excitatory synaptic transmission (as assessed by I/O relationships) and LTP at CA1 are reduced in TgCRND8 mice compared with wild-type mice (Kimura et al., 2012).
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Cognitive Impairment at 13
Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze, present by 3 months (Chishti et al., 2001).
Absent
-
Tangles at
Neurofibrillary tangles are absent (Chishti et al., 2001). Tau is hyperphosphorylated, nitrosylated and aggregated at 7-12 months especially in the neocortex, dentate gyrus, and the CA1 and CA3 areas of the hippocampus (Bellucci et al., 2007).
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
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APP | APP K670_M671delinsNL (Swedish), APP V717F (Indiana) | APP: Transgenic | Alzheimer's Disease | Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months . |
Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests. |