NEUROFIBRILLARY PATHOLOGY AND ALUMINUM IN ALZHEIMERS-DISEASE

Since the first reports of aluminum-induced neurofibrillary degenerati on in experimental animals, extensive studies have been performed to c larify the role played by aluminum in the pathogenesis of Alzheimer's disease (AD). Additional evidence implicating aluminum in AD includes elevated levels of aluminum in the AD brain, epidemiological data link ing aluminum exposure to AD, and interactions between aluminum and pro tein components in the pathological lesions of AD, i.e., neurofibrilla ry tangles (NFTs) and senile plaques (SPs). As most of this evidence i s circumstantial and some of it is not consistent in all reports, the role of aluminum in the pathogenesis of AD has remained controversial. However, the interaction of aluminum with altered forms of tau in the paired helical filaments (PHFs) of neurofibrillary lesions is highly likely to contribute to the formation of NFTs because (1) aluminum and abnormally phosphorylated tau (known as PHFs) are colocalized in NFTs , and (2) aluminum is known to preferentially interact with such phosp horylated proteins. Recently, we demonstrated that aluminum binds sele ctively to PHF tau, induces PHF tau to aggregate, and retards the in v ivo proteolysis of PHF tau. These data suggest that aluminum could ser ve as cofactor in the formation of NFTs by interacting with PHF-tau. T his review summarizes current understanding of how aluminum might cont ribute to the formation of neurofibrillary lesions from PHF tau in neu rons of the AD brain.