Neurofibrillary tangles in Alzheimer's disease and progressive supranuclear palsy: antigenic similarities and differences. Microtubule-associated protein tau antigenicity is prominent in all types of tangles

Abstract

The antigenic profile of neurofibrillary tangles (NFT) in Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT), progressive supranuclear palsy (PSP) and in non-demented aged humans was investigated by light and electron microscopic immunocytochemistry using antisera and monoclonal antibodies to tubulin, microtubule-associated proteins (MAP1, MAP2 and tau), neurofilament proteins and determinants unique to Alzheimer paired helical filaments (PHF). Antibodies to tau proteins labeled NFT in all cases investigated (AD, SDAT, PSP and non-demented aged humans). However, one monoclonal antibody to PHF recognized numerous tangles in AD/SDAT, but only a small minority of the PSP tangles. Antibodies to tubulin, MAP1, MAP2 and neurofilament proteins did not selectively stain NFT. Whereas pretreatment of sections with phosphatase was required for the detection of tangles with Tau-1 monoclonal antibody, digestion of sections with either phosphatase or pronase had no significant effect on the staining pattern obtained with the other antibodies. Our studies show that, as previously described for AD/SDAT, phosphorylated tau polypeptides are also a major antigenic determinant of tangles in PSP, indicating that tangle formation may follow a common pathogenetic pathway in neurofibrillary degenerations. There is, however, at least one epitope in AD/SDAT tangles which seems to be absent on, or at least inaccessible in, the 15-nm straight fibrils of PSP.