Cited by 274Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Augmented Senile Plaque Load in Aged Female β-Amyloid Precursor Protein-Transgenic Mice

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Callahan, Michael J., Lipinski, William J., Bian, Feng, Durham, Robert A., Pack, Amy, Walker, Lary C.·2001·The American Journal of Pathology

Abstract

Transgenic mice (Tg2576) overexpressing human beta-amyloid precursor protein with the Swedish mutation (APP695SWE) develop Alzheimer's disease-like amyloid beta protein (Abeta) deposits by 8 to 10 months of age. These mice show elevated levels of Abeta40 and Abeta42, as well as an age-related increase in diffuse and compact senile plaques in the brain. Senile plaque load was quantitated in the hippocampus and neocortex of 8- to 19-month-old male and female Tg2576 mice. In all mice, plaque burden increased markedly after the age of 12 months. At 15 and 19 months of age, senile plaque load was significantly greater in females than in males; in 91 mice studied at 15 months of age, the area occupied by plaques in female Tg2576 mice was nearly three times that of males. By enzyme-linked immunosorbent assay, female mice also had more Abeta40 and Abeta42 in the brain than did males, although this difference was less pronounced than the difference in histological plaque load. These data show that senescent female Tg2576 mice deposit more amyloid in the brain than do male mice, and may provide an animal model in which the influence of sex differences on cerebral amyloid pathology can be evaluated.

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  1. Selkoe DJ: Biology of ␤-amyloid precursor protein and the mecha- nism of Alzheimer disease. Alzheimer Disease, ed 2. Edited by RD Terry, R Katzman, KL Bick, SS Sisodia. Philadelphia, Lippincott Wil- liams and Wilkins, 1999, pp 293-310
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Authors
Callahan, M. J., Lipinski, W. J., Bian, F., Durham, R. A., Pack, A., & Walker, L. C.
Affiliations
Pfizer (United States) (US)
Corresponding author
Callahan, Michael J.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2001-03
Volume
158
Issue
3
Pages
1173-1177
ISSN
0002-9440 (ISSN-L)
OpenAlex
W2164192847
Cited by
274
References
30
Citations by year
2026: 4 · 2025: 7 · 2024: 8 · 2023: 5 · 2022: 8 · 2021: 14 · 2020: 10 · 2019: 14 · 2018: 9 · 2017: 10 · 2016: 9 · 2015: 17 · 2014: 15 · 2013: 16 · 2012: 10
FWCI
7.79
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Pfizer
  • Tulane University
  • York University
Topics
  • Health Sciences › Medicine › Physiology › 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
amyloid plaques, amyloid-beta, amyloid precursor protein, Tg2576 mice, sex differences, aging, Alzheimer's disease, amyloid deposition, hippocampus, neocortex, Aβ40, amyloid-beta 42
MeSH terms
Aging, Alzheimer Disease, Animals, Disease Models, Animal, Female, Hippocampus, Male, Mice, Transgenic, Peptide Fragments, Sex Factors, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neocortex, Mice, Plaque, Amyloid

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