Senile plaque neurites fail to demonstrate anti-paired helical filament and anti-microtubule-associated protein-tau immunoreactive proteins in the absence of neurofibrillary tangles in the neocortex

Abstract

Although much work has been directed recently towards unravelling the protein chemistry of neurofibrillary tangle (NFT) and senile plaque (SP) components in Alzheimer's disease, the pathogeneses of these lesions remains largely unknown and the problem of their relationship is unresolved. In particular, although paired helical filaments (PHF) have long been documented in SP neurites, we do not know if they are of pathogenetic relevance for the formation of the SP. To investigate the relationship between NFT and SP, we examined antigenic properties of proteins in SP neurites in neocortical tissues of patients with senile dementia of Alzheimer type, in the presence or absence of NFT in the same cortical area. We used two polyclonal antibodies directed against PHF and microtubule-associated protein (MAP)-tau and three monoclonal antibodies (MAbs) (RT97, BF10, 147) to phosphorylated epitopes of human neurofilament polypeptides, as well as the Gallyas silver impregnation method which specifically stains PHF in NFT and neurites. The main finding of our investigations consists in a differential pattern of immunoreactivity of SP neurites depending on the presence or absence of NFT in the neocortex. In the presence of NFT, there were numerous neuropil threads and SP neurites containing Gallyas-positive, as well as anti-PHF- and anti-tau-labelled material. In the absence of NFT in the neocortex there was a striking absence of any Gallyas-positive or PHF- and tau-immunoreactive structure in the cortical neuropil and in SP neurites, irrespective of the maturation stage of the SP.(ABSTRACT TRUNCATED AT 250 WORDS)