Associations of cortical astrogliosis with cognitive performance and dementia status.
We examined 204 decedents of the autopsy component of the Honolulu-Asia Aging Study, a longitudinal cohort study, who had been clinically assessed for dementia. A sensitive ELISA technique was used to quantify glial fibrillary acidic protein (GFAP), a marker for astrogliosis, in four specific cortical brain regions and assess associations between GFAP and 1) a measure of cognitive function, 2) several clinical dementia conditions, and 3) neuritic plaque (NP) and neurofibrillary tangle (NFT) formation. Cognitive function was inversely associated with GFAP in the occipital, parietal and temporal lobes, but not in the frontal lobe. This relationship remained significant when the contribution of NP and NFT counts was removed. Further, compared to brain samples from non-demented individuals, significantly greater GFAP levels were found in samples from individuals diagnosed with Alzheimer's disease, mixed dementia, and vascular mediated dementia. Because elevated levels of GFAP reflect astroglial responses to even subtle forms of neural damage, our data indicate that increments in GFAP may provide independent, supporting evidence for the damage underlying dementia, even in the absence of other evidence of neuropathology such as the presence of NPs or NFTs. Our findings underscore the need to look beyond standard neuropathological measures putatively linked to specific neuropathological conditions in efforts to identify common cellular and molecular processes that contribute to dementia.
Kashon
Michael L
ML
Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, WV 26505, USA. mkashon@cdc.gov
Ross
G Webster
GW
O'Callaghan
James P
JP
Miller
Diane B
DB
Petrovitch
Helen
H
Burchfiel
Cecil M
CM
Sharp
Dan S
DS
Markesbery
William R
WR
Davis
Daron G
DG
Hardman
John
J
Nelson
James
J
White
Lon R
LR
D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D003072:Cognition Disorders / Q000473:pathology*; D015331:Cohort Studies; D003704:Dementia / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009778:Occipital Lobe / Q000378:metabolism / Q000473:pathology; D010296:Parietal Lobe / Q000378:metabolism / Q000473:pathology; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D012720:Severity of Illness Index; D013702:Temporal Lobe / Q000378:metabolism / Q000473:pathology
D005904:Glial Fibrillary Acidic Protein