Glial fibrillary acidic protein and βA4 protein deposits in temporal lobe of aging brain and senile dementia of the Alzheimer type: Relation with the cognitive state and with quantitative studies of senile plaques and neurofibrillary tangles

Abstract

The aim of this study was to compare brain glial fibrillary acidic protein (GFAP) levels to the modifications of cognitive functions (Blessed test score [BTS]), the density of the main neuropathological lesions (senile plaques [SP] and neurofibrillary tangles [NFT]), and the density of the two main subtypes of βA4 deposits (classic plaques and diffuse deposits) in a series of patients with normal aging and senile dementia of the Alzheimer type of various degrees of severity. GFAP levels (enzymelinked immunosorbent assay [ELISA] technique) and the densities of changes were measured in the temporal lobe of 12 women over 75 years of age. Under these conditions, the ELISA assay could determine GFAP in brain homogenates (aqueous‐Triton buffer soluble extract) in a range from 2.5 ng to 600 ng per assay. Least affected patients (with a BTS of 19 and over) all ranged below 60 μg/mg protein. Most affected patients (with a BTS under 6) ranged above 150 μg/mg protein. However, interindividual variations were wide. A significant correlation between the BTS and the amount of GFAP could be found only when using the non parametric test of Spearman. There was a significant positive correlation between the amount of GFAP and the density of (1) SP, (2) NFT both revealed by Bodian's silver stain, and (3) classic βA4 plaques shown by immunocytochemistry. On the contrary, no correlation was observed with diffuse βA4 deposits. One case with very large amounts of diffuse βA4 deposits without SP or NFT showed no associated GFAP reactivity. This suggests that GFAP production is a critical event in the formation of classic SP.