Astrocyte phenotype in relation to Alzheimer‐type pathology in the ageing brain
Open accessAbstract
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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Reactive morphological changes are driven by an increase of intermediate filament proteins such as GFAP and vimentin.
“Finely tuned morphological changes are driven by an increase of intermediate filament proteins, such as GFAP and vimentin [15, 38, 41, 42, 43], which not only provide mechanical sustenance for the maintenance of astrocyte shape, but also support the functional profile of reactive astrocytes through transcriptional modulation of target genes involved in astroglial and microglial responsiveness [44,”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [41]
GFAP increases in parallel with Braak stages in AD and correlates with greater astrocyte reactivity.
“GFAP increases in parallel with Braak stages in AD and correlates with greater astrocyte reactivity [41].”
From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [41]
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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
- Open access
- Licence
- 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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