Population variation in glial fibrillary acidic protein levels in brain ageing: relationship to Alzheimer-type pathology and dementia.
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 epsilon4 was associated with slightly increased GFAP levels (not significant) for given amyloid beta protein loads.


CONCLUSIONS
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.
Academic Unit of Pathology, University of Sheffield Medical School, Sheffield, UK. s.wharton@sheffield.ac.uk
S B
SB
Wharton
J P
JP
O'Callaghan
G M
GM
Savva
J A R
JA
Nicoll
F
F
Matthews
J E
JE
Simpson
G
G
Forster
P J
PJ
Shaw
C
C
Brayne
P G
PG
Ince
D000368:Aged; D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000378:metabolism; D001253:Astrocytes / Q000473:pathology; D001921:Brain / Q000254:growth & development*; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology*; D015331:Cohort Studies; D003704:Dementia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D005911:Gliosis / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D005904:Glial Fibrillary Acidic Protein