Associations of cortical astrogliosis with cognitive performance and dementia status

Article type: Research Article

Authors: Kashon, Michael L.^{a; *} | Ross, G. Webster^{b; c; d} | O'Callaghan, James P.^a | Miller, Diane B.^a | Petrovitch, Helen^{b; c; d} | Burchfiel, Cecil M.^a | Sharp, Dan S.^a | Markesbery, William R.^e | Davis, Daron G.^e | Hardman, John^c | Nelson, James^d | White, Lon R.^{b; c; d}

Affiliations: [a] Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, WV 26505, USA, (MLK, JPO, DBM, CMBD SS) | [b] Department of Veterans Affairs, Honolulu, HI, USA | [c] Department of Medicine, University of Hawaii, John A. Burns School of Medicine, Honolulu, HI 96826, USA | [d] Pacific Health Research Institute, Honolulu, HI 96813 (GWR, HP, JN, LRW); Kuakini Medical Center/Honolulu-Asia Aging Study, Honolulu, HI 96817, USA | [e] Department of Pathology and the Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40506, USA

Correspondence: [*] Corresponding author: Michael L. Kashon, PhD, Centers for Disease Control and Prevention-NIOSH, Health Effect Laboratory Division, 1095 Willowdale Road, Morgantown, WV 26505, USA. Tel.: +1 304 285 6209; Fax: +1 304 285 6112; E-mail: [email protected].

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.

Keywords: astrogliosis, GFAP, cognitive performance, dementia, Alzheimer's disease, neurotic plaque, neurofibrillary tangle

DOI: 10.3233/JAD-2004-6604

Journal: Journal of Alzheimer's Disease, vol. 6, no. 6, pp. 595-604, 2004