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Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype
Simpson JE, Ince PG, Shaw PJ, Heath PR, Raman R, Garwood CJ, Gelsthorpe C, Baxter L et al.. Neurobiology of aging, 2011-06-25
Topic: Amyloid, tau and blood-test diagnosis
Astrocytes contribute to a variety of functions in the brain, including homeostasis, synapse formation, plasticity, and metabolism. Astrocyte dysfunction may disrupt their normal role, including neuronal support, thereby contributing to neurodegenerative pathologies, including Alzheimer's disease (AD). To understand the role of astrocytes in the pathogenesis of age-related disorders, we isolated astrocytes by laser capture microdissection, using glial fibrillary acidic protein (GFAP) as a marker, and characterized the astrocyte transcriptome at different Braak neurofibrillary tangle stages in postmortem temporal cortex samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) cohort, using microarray analysis. The largest number of significant, differentially expressed genes were identified when the expression profile of astrocytes from isocortical stages of neurofibrillary tangle pathology (Braak stages V-VI) were compared with entorhinal stages (Braak stages I-II). Dysregulation of genes associated with the actin cytoskeleton, proliferation, apoptosis, and ubiquitin-mediated proteolysis occurred at low Braak stages, while altered regulation of intracellular signaling pathways, including insulin, phosphatidylinositol 3-kinase (PI3K)/Akt, and mitogen-activated protein kinase (MAPK) pathways were primarily associated with high levels of Alzheimer-type pathology, and occurred at lower Braak stages in individuals with the APOEε4 allele. Our findings implicate astrocyte dysfunction in the pathogenesis of neurodegenerative pathology in the aging brain, and provide a basis for future candidate studies based on specific pathways.
Key findings
- The largest number of significant, differentially expressed genes were identified when the expression profile of astrocytes from isocortical stages of neurofibrillary tangle pathology (Braak stages V-VI) were compared with entorhinal stages (Braak stages I-II).
- Dysregulation of genes associated with the actin cytoskeleton, proliferation, apoptosis, and ubiquitin-mediated proteolysis occurred at low Braak stages, while altered regulation of intracellular signaling pathways, including insulin, phosphatidylinositol 3-kinase (PI3K)/Akt, and mitogen-activated protein kinase (MAPK) pathways were primarily associated with high levels of Alzheimer-type pathology, and occurred at lower Braak stages in individuals with the APOEε4 allele.
- Our findings implicate astrocyte dysfunction in the pathogenesis of neurodegenerative pathology in the aging brain, and provide a basis for future candidate studies based on specific pathways.
Why it matters
This study characterized gene expression in astrocytes from postmortem brain tissue at different stages of neurofibrillary tangle pathology. It describes changes in astrocyte genes related to Alzheimer pathology and APOE genotype, and reports no treatment, cure or prevention.
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Study details
- Evidence strengthModerate
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Neurobiology of aging) |
| Journal's citation record | 3 / 4 | Neurobiology of Aging: journal h-index 263 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 193 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.4 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 3 / 6 | Cited 6.4× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 5 other studies in this library |
| Still being cited | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Stephen B. Wharton: h-index 63 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Cambridge: institution h-index 1,973 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21705112) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
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May need a subscription Unpaywall, Europe PMC and OpenAlex found no free copy of the full text (checked 10 Oct 2026), so the publisher may charge for it. The PubMed abstract is free.
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APA 7th
Simpson, J. E., Ince, P. G., Shaw, P. J., Heath, P. R., Raman, R., Garwood, C. J., et al. (2011). Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2011.04.013
Vancouver
Simpson JE, Ince PG, Shaw PJ, Heath PR, Raman R, Garwood CJ, et al. Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype. Neurobiology of aging. 2011. doi:10.1016/j.neurobiolaging.2011.04.013. PMID: 21705112.
BibTeX
@article{simpson2011-21705112,
author = {Simpson, J. E. and Ince, P. G. and Shaw, P. J. and Heath, P. R. and Raman, R. and Garwood, C. J. and Gelsthorpe, C. and Baxter, L. and others},
title = {{Microarray analysis of the astrocyte transcriptome in the aging brain: relationship to Alzheimer's pathology and APOE genotype}},
journal = {Neurobiology of aging},
year = {2011},
doi = {10.1016/j.neurobiolaging.2011.04.013},
pmid = {21705112},
url = {https://doi.org/10.1016/j.neurobiolaging.2011.04.013}
}
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