Skip to main content

Research Repository

Advanced Search

Microarray analysis of the astrocyte transcriptome in the aging brain: Relationship to Alzheimer's pathology and APOE genotype

Simpson, Julie E.; Ince, Paul G.; Shaw, Pamela J.; Heath, Paul R.; Raman, Rohini; Garwood, Claire J.; Gelsthorpe, Catherine; Baxter, Lynne; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Wharton, Stephen B.

Authors

Julie E. Simpson

Paul G. Ince

Pamela J. Shaw

Paul R. Heath

Rohini Raman

Claire J. Garwood

Catherine Gelsthorpe

Lynne Baxter

Gillian Forster

Carol Brayne

Stephen B. Wharton



Abstract

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. © 2011 Elsevier Inc.

Citation

Simpson, J. E., Ince, P. G., Shaw, P. J., Heath, P. R., Raman, R., Garwood, C. J., …Wharton, S. B. (2011). Microarray analysis of the astrocyte transcriptome in the aging brain: Relationship to Alzheimer's pathology and APOE genotype. Neurobiology of Aging, 32(10), 1795-1807. https://doi.org/10.1016/j.neurobiolaging.2011.04.013

Journal Article Type Article
Publication Date Oct 1, 2011
Deposit Date Dec 8, 2023
Journal Neurobiology of Aging
Print ISSN 0197-4580
Electronic ISSN 1558-1497
Publisher Elsevier
Volume 32
Issue 10
Pages 1795-1807
DOI https://doi.org/10.1016/j.neurobiolaging.2011.04.013
Public URL https://hull-repository.worktribe.com/output/4454832