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Cognitive correlates of Aβ deposition in male and female mice bearing amyloid precursor protein and presenilin-1 mutant transgenes
Abstract
Several transgenic mouse models of Alzheimer's disease (AD) have been developed that exhibit beta-amyloid (Abeta) neuropathology and behavioural deficits. However, not all studies have investigated the relationship between the development of cognitive impairment and neuropathology. Therefore, temporal changes in cognition were investigated in male and female double-mutant APPswexPS1.M146V (TASTPM) transgenic mice using an object recognition test and correlated with the development of cerebral Abeta neuropathology. Both male and female TASTPM mice exhibited similar significant cognitive impairment at 6, 8 and 10 months of age in the object recognition test, compared to wild-type littermates. There was no such cognitive impairment at 3 or 4 months of age. Quantitative immunohistochemistry using a battery of Abeta antibodies demonstrated that cerebral Abeta deposition was first apparent in 3-month-old mice, and it increased with age. The early appearance of cerebral Abeta deposits in the double-transgenic TASTPM mice supports the evidence that mutations in the PS1 gene accelerate Abeta deposition. The cerebral Abeta load was greater in female than in male TASTPM mice at all ages investigated. In the electron microscope, mature Abeta plaques comprising a fibrillar core surrounded by degenerating neurites and reactive glia were first observed in the cortex of TASTPM mice at 6 months of age, the same age at which cognitive impairment became apparent. These results suggest that the cognitive impairment in TASTPM mice is related to the disruption of neural connectivity and not simply Abeta deposition, which first occurs 3 months earlier.
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“For instance, the TASTPM mouse model of AD has amyloid plaques and demonstrates memory deficits, but does not show neurofibrillary tangles (101).”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [101]
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Additional file 11 of Sex specific molecular networks and key drivers of Alzheimer’s disease
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Additional file 2 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598350
Additional file 13 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598383
Additional file 1 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598347
Additional file 5 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598359
Additional file 23 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598413
Additional file 20 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598404
Additional file 25 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598419
Additional file 4 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598356
Additional file 7 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598365
Yuan, Y., Li, J., Zhang, N., Fu, P., Jing, Z., Yu, C., Zhao, D., Hao, W., & Zhou, C. (2021) · Figshare · doi:10.6084/m9.figshare.13634332
Additional file 26 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598422
Additional file 18 of Sex specific molecular networks and key drivers of Alzheimer’s disease
Guo, L., Cao, J., Hou, J., Li, Y., Huang, M., Zhu, L., Zhang, L., Lee, Y., Duarte, M. L., Zhou, X., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26598398
Metadata
- Authors
- Howlett, D. R., Richardson, J. C., Austin, A., Parsons, A. A., Bate, S. T., Davies, D. C., & Gonzalez, M. I.
- Affiliations
- GlaxoSmithKline (United Kingdom) (GB)
- St George's Hospital (GB)
- Corresponding author
- Howlett, David R
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2004-08
- Volume
- 1017
- Issue
- 1-2
- Pages
- 130-136
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2048622057
- Cited by
- 212
- References
- 41
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 21 · 2023: 8 · 2022: 7 · 2021: 10 · 2020: 12 · 2019: 6 · 2018: 17 · 2017: 5 · 2016: 6 · 2015: 13 · 2014: 6 · 2013: 14 · 2012: 15
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, amyloid-beta deposition, presenilin 1 mutations, amyloid precursor protein mutations, cognitive impairment, object recognition, sex differences, amyloid plaques, neuronal connectivity
- MeSH terms
- Age Factors, Alzheimer Disease, Analysis of Variance, Animals, Behavior, Animal, Cerebral Cortex, Disease Models, Animal, Female, Immunohistochemistry, Male, Membrane Proteins, Mice, Transgenic, Microscopy, Electron, Mutation, Neuropsychological Tests, Sex Characteristics, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice, Presenilin-1, Plaque, Amyloid
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