title: Interaction of aluminum with paired helical filament tau is involved in neurofibrillary pathology of Alzheimer's disease.
abstract: Since the first reports of aluminum-induced neurofibrillary degeneration in experimental animals, extensive studies have been performed to clarify 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, epidemiologic data linking aluminum exposure to AD, and interactions between aluminum and protein components in the pathologic lesions of AD, i.e., neurofibrillary tangles (NFTs) and senile plaques. As most of this evidence is 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 PHF tau) are colocalized in NFTs, and (2) aluminum is known to preferentially interact with such phosphorylated proteins. Recently, it was demonstrated that aluminum binds selectively to PHF tau, induces PHF tau to aggregate, and retards the in vivo proteolysis of PHF tau. These data suggest that aluminum could serve as a cofactor in the formation of NFTs by interacting with PHF tau. This review summarizes the current understanding of how aluminum might contribute to the formation of neurofibrillary lesions from PHF tau in neurons of the AD brain.
authors.affiliation: Department of Neurological Science, Tohoku University of Medical School, Sendai, Japan.
authors.forename: R W
authors.initials: RW
authors.lastname: Shin
mesh_terms: D000535:Aluminum / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D004347:Drug Interactions; D006801:Humans; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000502:physiology*
chemical_list: D016875:tau Proteins; D000535:Aluminum