APOLIPOPROTEIN-E INTERACTION WITH THE NEUROFIBRILLARY TANGLES AND SENILE PLAQUES IN ALZHEIMER-DISEASE - IMPLICATIONS FOR DISEASE PATHOGENESIS

Apolipoprotein E (ApoE) genotype is a significant risk factor for the development of Alzheimer disease (AD) and the ApoE protein is associat ed with senile plaques (SP) and neurofibrillary tangles (NFT), the pat hological lesions of AD. Despite this data, the relevance of ApoE to t he disease pathogenesis is unknown. In this study we sought to underst and the role that ApoE protein could play in the pathogenesis of AD. U sing an in situ binding technique, we showed that ApoE bound avidly to SP and NFT in diseased brain. Molecular characterization of ApoE bind ing suggested that binding to NFT was mediated by tau, the main protei n component of NFT, and that ApoE binding to SP was mediated by amyloi d-beta, the main protein component of SP. There was no significant dif ference in binding or binding characteristics between the different Ap oE isoforms, ApoE(3) and ApoE(3). These findings suggest that the inte raction of ApoE with tau and amyloid-beta proteins in AD could play a important role in the formation of NFT and SP, respectively, contribut ing to the pathogenesis of AD. (C) 1995 Academic Press Inc.