Population Variation in Glial Fibrillary Acidic Protein Levels in Brain Ageing: Relationship to Alzheimer-Type Pathology and DementiaWharton S.B. · O’Callaghan J.P. · Savva G.M. · Nicoll J.A.R. · Matthews F. · Simpson J.E. · Forster G. · Shaw P.J. · Brayne C. · Ince P.G.
aCenters for Disease Control and Prevention-NIOSH, Morgantown, W.Va., USA; bAcademic Unit of Pathology and cAcademic Unit of Neurology, University of Sheffield, Sheffield, dDepartment of Public Health and Primary Care and eMRC Biostatistics Unit, Institute of Public Health, University of Cambridge, Cambridge, and fDivision of Clinical Neurosciences, University of Southampton, Southampton, UK
Background: The cellular pathology of astrocytes in brain ageing and their role in modulating the brain’s response to neurodegenerative pathology remain incompletely understood. Methods: Using quantitative ELISA, we have investigated glial fibrillary acidic protein (GFAP) expression in the population-based neuropathology cohort of the Medical Research Council Cognitive Function and Ageing Study to determine: (1) the population variation in the astroglial hypertrophic response, (2) its relationship to the presence of Alzheimer-type pathology, and (3) its association with cognition. Results: Increasing GFAP was found with increasing Braak stage, levels increasing even at early stages. Within Braak stages, GFAP did not differ between demented and non-demented individuals, but there was greater variance in GFAP in the demented. Possession of ApoE ε4 was associated with slightly increased GFAP levels (not significant) for given amyloid β protein loads. Conclusion: In a population-based sample, increasing gliosis precedes development of Alzheimer lesions. Population variation in GFAP with varying Alzheimer lesion burdens suggests that they are not the only driver for astrogliosis. GFAP was not independently predictive of dementia, but the variation in astrocytic responses may be a factor modulating brain responses to neurodegenerative pathology.
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Accepted: February 23, 2009
Published online: May 7, 2009
Number of Print Pages : 9
Number of Figures : 4, Number of Tables : 1, Number of References : 50
Dementia and Geriatric Cognitive Disorders
Vol. 27, No. 5, Year 2009 (Cover Date: June 2009)
Journal Editor: Chan-Palay V. (New York, N.Y.)
ISSN: 1420-8008 (Print), eISSN: 1421-9824 (Online)
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