title: Neurofibrillary pathology and aluminum in 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, epidemiological data linking aluminum exposure to AD, and interactions between aluminum and protein components in the pathological lesions of AD, i.e., neurofibrillary tangles (NFTs) and senile plaques (SPs). 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, we 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 cofactor in the formation of NFTs by interacting with PHF tau. This review summarizes 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 Sciences, Tohoku University, Sendai, Japan.
authors.forename: R W
authors.initials: RW
authors.lastname: Shin
authors.forename: V M
authors.initials: VM
authors.lastname: Lee
authors.forename: J Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000535:Aluminum / Q000378:metabolism* / Q000633:toxicity*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology*
chemical_list: D000535:Aluminum