Cited by 247Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Time Course of the Development of Alzheimer-like Pathology in the Doubly Transgenic PS1+APP Mouse

Gordon, Marcia N., Holcomb, Leigh A., Jantzen, Paul T., DiCarlo, Giovanni, Wilcock, Donna, Boyett, Kristal W., Connor, Karen, Melachrino, Jason +2 more·2002·Experimental Neurology

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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Crossref · 10.1006/exnr.2001.7754

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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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