title: Associations of cortical astrogliosis with cognitive performance and dementia status.
abstract: 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.
authors.affiliation: Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, WV 26505, USA. mkashon@cdc.gov
authors.forename: Michael L
authors.initials: ML
authors.lastname: Kashon
authors.forename: G Webster
authors.initials: GW
authors.lastname: Ross
authors.forename: James P
authors.initials: JP
authors.lastname: O'Callaghan
authors.forename: Diane B
authors.initials: DB
authors.lastname: Miller
authors.forename: Helen
authors.initials: H
authors.lastname: Petrovitch
authors.forename: Cecil M
authors.initials: CM
authors.lastname: Burchfiel
authors.forename: Dan S
authors.initials: DS
authors.lastname: Sharp
authors.forename: William R
authors.initials: WR
authors.lastname: Markesbery
authors.forename: Daron G
authors.initials: DG
authors.lastname: Davis
authors.forename: John
authors.initials: J
authors.lastname: Hardman
authors.forename: James
authors.initials: J
authors.lastname: Nelson
authors.forename: Lon R
authors.initials: LR
authors.lastname: White
mesh_terms: 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
chemical_list: D005904:Glial Fibrillary Acidic Protein