Alzheimer's disease: exposure of neurofilament immunoreactivity in SDS-insoluble paired helical filaments

Abstract

In Alzheimer's disease, neurofibrillary tangles (NFT) react with both antibodies to paired helical filaments (PHF) and certain antibodies to neurofilaments, for example, monoclonal RT97 against the 200,000 mol. wt. neurofilament protein. After isolating NFT by extraction in sodium dodecyl sulfate (SDS), PHF antibodies remain reactive while RT97 weakly stains only a minority of the extracted tangles. We now show that isolated NFT initially unreactive with RT97 apparently develop exposed antigenic sites following incubation under denaturing conditions. Our results suggest that at least one neurofilament epitope is buried in the SDS-insoluble PHF fiber and that conformational changes in PHF proteins allow its exposures.