Identification and Characterization of Modified Forms of Tau in Brains with Alzheimer’s Disease
In Alzheimer’s disease affected brain, neurons are characterized by bundles of paired helical filaments (PHF) in perikarya and neurites (1). Antibodies raised against PHF enriched preparation were shown to react with microtubule associated protein tau, and antibodies to tau bind PHF (2,3,4). With few exceptions most of the antibodies to other cytoskeletal proteins such as neurofilament proteins or microtubule associated protein 2 have no reactivity with PHF. These observations lead to the suggestion that tau is a major antigenic component of PHF (5). PHF enriched preparations prepared by some methods were insoluble in SDS (6,7), while by other methods were soluble (8). Peptide fragments generated by proteolytic digestion of PHF enriched samples contained amino acid sequences similar to the carboxyl terminal half of the tau proteins (7,9). The reaction of PHF to two anti-tau antibodies has been demonstrated to require a pretreatment of PHF with phosphatase (2,10). These findings provided the basis for the suggestion that tau is a component of PHF and that the phosphorylation of PHF-related tau is different from normal tau. However, it is uncertain whether the abnormality of PHF-related tau is limited to phosphorylation, and if all regions of the tau molecule are incorporated into PHF. Additional information on the biochemical and immunochemical properties of PHF proteins is important for studying the abnormality in PHF.
KeywordsTerminal Region Microtubule Assembly Proteolytic Digestion Paired Helical Filament Paired Helical Filament
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