Time Course of the Development of Alzheimer-like Pathology in the Doubly Transgenic PS1+APP Mouse
Abstract
Doubly transgenic mice expressing both a mutated amyloid precursor protein and a mutated presenilin-1 protein accumulate A(beta) deposits as they age. The early A(beta) deposits were found to be primarily composed of fibrillar A(beta) and resembled compact amyloid plaques. As the mice aged, nonfibrillar A(beta) deposits increased in number and spread to regions not typically associated with amyloid plaques in Alzheimer's disease. The fibrillar, amyloid-containing deposits remained restricted to cortical and hippocampal structures and did not increase substantially beyond the 12-month time point. Even at early time points, the fibrillar deposits were associated with dystrophic neurites and activated astrocytes expressing elevated levels of glial fibrillary acidic protein. Microglia similarly demonstrated increased staining for complement receptor-3 in the vicinity of A(beta) deposits at early time points. However, when MHC-II staining was used to assess the degree of microglial activation, full activation was not detected until mice were 12 months or older. Overall, the regional pattern of A(beta) staining resembles that found in Alzheimer disease; however, a progression from diffuse A(beta) to more compact amyloid deposits is not observed in the mouse model. It is noted that the activation of microglia at 12 months is coincident with the apparent stabilization of fibrillar A(beta) deposits, raising the possibility that activated microglia might clear fibrillar A(beta) deposit…
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Animal models of amyloid pathology offer an experimental platform for studying Alzheimer's disease.
“Animal models of amyloid pathology offer an experimental platform to studying AD (Gordon et al., 2002).”
From Early Alterations in Functional Connectivity and White Matter Structure in a Transgenic Mouse Model of Cerebral Amyloidosis (2014) · cites this paper as Gordon et al., 2002
Astrocyte alterations precede microglia reactivity in AD.
“In fact, based on the kinetics of appearance of reactivity markers, previous studies concluded that astrocyte alterations would precede microglia reactivity (Chun et al., 2018; Gordon et al., 2002; Tournier et al., 2020).”
From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Gordon et al., 2002
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“DOI:10.1523/JNEUROSCI.4762-13.2014 Copyright © 2014 the authors 0270-6474/14/3413780-10$15.00/0 Animal models of amyloid pathology offer an experimental platform to studying AD (Gordon et al., 2002).”
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- Authors
- Gordon, M. N., Holcomb, L. A., Jantzen, P. T., DiCarlo, G., Wilcock, D., Boyett, K. W., Connor, K., Melachrino, J., O'Callaghan, J. P., & Morgan, D.
- Affiliations
- University of South Florida (US)
- National Institute for Occupational Safety and Health (US)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 173
- Issue
- 2
- Pages
- 183-195
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2152286012
- Cited by
- 247
- References
- 42
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 6 · 2020: 12 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 16 · 2012: 15
- FWCI
- 11.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG018478, AG 15490, R01AG015490, AG18478)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, amyloid plaques, presenilin 1, amyloid precursor protein, microglial activation, complement receptor 3, MHC class II, astrocytes, glial fibrillary acidic protein, dystrophic neurites, mouse model
- MeSH terms
- Aging, Alzheimer Disease, Animals, Histocompatibility Antigens Class II, Astrocytes, Brain, Brain Stem, Cell Count, Disease Models, Animal, Glial Fibrillary Acidic Protein, Immunohistochemistry, Membrane Proteins, Mice, Transgenic, Neurons, Receptors, Complement, Neurites, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, Microglia, Disease Progression, Mice, Presenilin-1
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