TAU IN ALUMINUM-INDUCED NEUROFIBRILLARY TANGLES

Aluminum is a neurotoxin and in susceptible species induces a neurofib rillary pathology characterized by argentophilic masses in neuronal pe rikarya and in axonal spheroids. These inclusions are known to contain neurofilament proteins. Using immunocytochemistry and immunoblotting, we demonstrate that tau is a component of these aluminum-induced neur ofibrillary tangles (AI-NFTs) in rabbits. Double-label immunocytochemi stry experiments reveal co-localization of phosphorylated neurofilamen ts (using SMI31) and tau (using tau-1, tau-5, AT8, and PHF-1) in the p erikaryal AI-NFTs. Nonphosphorylated tau (detected using tau-1) occupi es a smaller area of the AI-NFT than the total pool of tau proteins (d etected using tau-5). The area of fetal tau and non-phosphorylated tau immunolabeling in the AI-NFT increases as the size of the AI-NFT (i.e ., the proportion of cell area occupied by the AI-NFT) increases. The proportion of cell area (outside of the AI-NFT) occupied by tau (as in dicated by tau-5) decreases as the area of tau in the AI-NFT increases and as the size of the AI-NFT in the cell increases. Immunoblotting e xperiments demonstrate 1) the specificity of the tau antibody labeling and verify a lack of cross-reactivity of the tau-5 antibody to neurof ilament proteins in rabbit tissue; and 2) no alterations in the levels of tau resulting from aluminum-treatment. These data suggest that as the size of the AI-NFT in a cell increases there is less tau in the ne uronal perikarya. Therefore, there may be less tau in the perikarya av ailable to perform normal functions such as microtubule polymerization and stabilization. Tau and neurofilament proteins are perturbed in a number of neurodegenerative disorders such as Alzheimer's disease, dif fuse Lewy body disease, and Parkinson's disease. Aluminum-induced neur ofibrillary pathology may provide a model to study perturbations in ta u and neurofilaments, their phosphorylation and deposition into pathol ogical inclusions. (C) 1997 Inter Press, Inc.