Astrocytosis, βA4-protein deposition and paired helical filament formation in Alzheimer's disease

Abstract

Alzheimer's disease (AD) temporal cortex (Brodmann area 22) was investigated using stains for astrocytes (GFAP immunohistochemistry), paired helical filaments (Gallyas silver impregnation) and βA4-protein deposition (βA4-protein immunohistochemistry). Paired helical filament formation (PHF), as demonstrated by neurofibrillary tangle (NFT) and neuritic plaque (NP) density, was greatest in the pyramidal cell layers III and V. βA4-protein deposition was greatest in layer III but was present in all neocortical layers. In a regression analysis, astrocyte density was significantly correlated with βA4-protein deposition ( R 2 = 0.35, P = 0.02). Astrocyte density was also positively correlated with PHF formation as measured by NFT ( R 2 = 0.16, P = 0.14) and NP ( R 2 = 0.25, P = 0.06) density, but this was less significant. This quantitative study demonstrates that both βA4-protein deposits and PHF formation are positively correlated with the severity of astrocytosis and that damage to the brain parenchyma in temporal cortex in AD may be slightly more strongly associated with βA4-protein deposition than paired helical filament formation. These results demonstrate the close association of astrocytes with βA4-protein deposition and neuritic change in AD.