Population variation in glial fibrillary acidic protein levels in brain ageing: relationship to Alzheimer-type pathology and dementia
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 4 was associated with slightly increased GFAP levels (not significant) for given amyloid 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
465-473
Wharton, S.B.
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O' Callaghan, J.P
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Savva, G.M
9137192b-c302-4c2c-be31-b62935bfcae6
Nicoll, J.A
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Matthews, F
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Simpson, J.E.
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Foster, G
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Shaw, P.J
04188840-ff58-4e88-b19a-d4b1bdf7adf3
Brayne, C
2d23a2e3-3a06-42f5-be1f-7f15f6e4c8ad
MRC Cognitive Function and Ageing Neuropathology Study Group
June 2009
Wharton, S.B.
f94ebc06-35d9-4a42-bf06-0f3c2f1151b0
O' Callaghan, J.P
9294add7-fda0-495a-9060-0650f6ffa7a0
Savva, G.M
9137192b-c302-4c2c-be31-b62935bfcae6
Nicoll, J.A
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Matthews, F
7a205b69-d2aa-4acb-bb55-8300466cc182
Simpson, J.E.
6d6e4297-618f-40a3-be3b-53f3f4d9242d
Foster, G
200654f5-0582-45cf-9fcc-a4b38a724f50
Shaw, P.J
04188840-ff58-4e88-b19a-d4b1bdf7adf3
Brayne, C
2d23a2e3-3a06-42f5-be1f-7f15f6e4c8ad
Wharton, S.B., O' Callaghan, J.P, Savva, G.M, Nicoll, J.A, Matthews, F, Simpson, J.E., Foster, G, Shaw, P.J and Brayne, C
,
MRC Cognitive Function and Ageing Neuropathology Study Group
(2009)
Population variation in glial fibrillary acidic protein levels in brain ageing: relationship to Alzheimer-type pathology and dementia.
Dementia and Geriatric Cognitive Disorders, 27 (5), .
(doi:10.1159/000217729).
Abstract
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 4 was associated with slightly increased GFAP levels (not significant) for given amyloid 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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Published date: June 2009
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Local EPrints ID: 79361
URI: http://eprints.soton.ac.uk/id/eprint/79361
ISSN: 1420-8008
PURE UUID: 514d7c7b-68a8-4568-a12c-70a2d0bf5e3c
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Date deposited: 15 Mar 2010
Last modified: 14 Mar 2024 02:46
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Author:
S.B. Wharton
Author:
J.P O' Callaghan
Author:
G.M Savva
Author:
F Matthews
Author:
J.E. Simpson
Author:
G Foster
Author:
P.J Shaw
Author:
C Brayne
Corporate Author: MRC Cognitive Function and Ageing Neuropathology Study Group
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