Cited by 381Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Astrocyte phenotype in relation to Alzheimer‐type pathology in the ageing brain

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Simpson, J.E., Ince, P.G., Lace, G., Forster, G., Shaw, P.J., Matthews, F., Savva, G., Brayne, C. +1 more·2010·Neurobiology of Aging

Abstract

Astrocyte pathology occurs in association with Alzheimer's disease (AD) and in brain ageing, but is poorly characterised. We sought to define the detailed cellular pathology of astrocytes, the extent of population variation and the relationship to Alzheimer-type changes in a population-based cohort. Three staining patterns were associated with GFAP and excitatory amino acid transporter 2 (EAAT2): minimal, moderate or extensive immunoreactivity. GFAP and EAAT2 expression were inversely related (p=0.015), with trends to increased expression of GFAP (p=0.019) and decreased expression of EAAT2 (p=ns) with increasing Braak stage. GFAP and EAAT2 correlated incompletely with beta-amyloid and tau immunoreactivity. However, gliosis increased with increasing burden of neuritic (p=0.011), but not diffuse (p=ns), plaques. Double-staining revealed distinct subsets of astrocytes; GFAP(+)EAAT(-), GFAP(-)EAAT(+), or GFAP(+)EAAT(+). In contrast to the variation in GFAP and EAAT2, levels of EAAT1 and S100B showed consistent staining patterns. Alzheimer-type pathology only partially explains the variation in gliosis and astrocyte functional markers, suggesting that other factors contribute to the population variance in astrocyte pathology.

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Crossref · 10.1016/j.neurobiolaging.2008.05.015

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Authors
Simpson, J. E., Ince, P. G., Lace, G., Forster, G., Shaw, P. J., Matthews, F., Savva, G., Brayne, C., & Wharton, S. B.
Affiliations
  • University of Sheffield (GB)
  • University of Cambridge (GB)
Corresponding author
Wharton, S.B.
Venue
Neurobiology of Aging
Publisher
Elsevier BV
Published
2010-04
Volume
31
Issue
4
Pages
578-590
ISSN
0197-4580 (ISSN-L)
OpenAlex
W2064119008
Cited by
381
References
8
Citations by year
2026: 10 · 2025: 23 · 2024: 24 · 2023: 34 · 2022: 22 · 2021: 35 · 2020: 27 · 2019: 17 · 2018: 35 · 2017: 24 · 2016: 9 · 2015: 30 · 2014: 16 · 2013: 16 · 2012: 13
FWCI
10.38
Type
journal article
Language
en
Locations
  • Neurobiology of Aging (publishedVersion)
  • PubMed (publishedVersion)
  • Repository@Hull (Worktribe) (University of Hull) (submittedVersion, cc-by)
Funders
  • Medical Research Council
  • Alzheimer's Research Trust
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
astrocyte phenotype, Alzheimer's disease, brain aging, glial fibrillary acidic protein, GLT-1, GLAST, S100B, gliosis, Braak stages, amyloid-beta, tau protein, neuritic plaques, diffuse plaques, astrocyte heterogeneity, glutamate transporters
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Astrocytes, Brain, Female, Glial Fibrillary Acidic Protein, Gliosis, Humans, Immunohistochemistry, Longitudinal Studies, Male, Nerve Growth Factors, S100 Proteins, Nerve Tissue Proteins, Phenotype, Predictive Value of Tests, Prospective Studies, Severity of Illness Index, Cohort Studies, Biomarkers, Amyloid beta-Peptides, tau Proteins, Excitatory Amino Acid Transporter 1, Excitatory Amino Acid Transporter 2, Plaque, Amyloid, S100 Calcium Binding Protein beta Subunit

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