Mutation-specific functional impairments in distinct Tau isoforms of hereditary FTDP-17

Tau proteins aggregate as cytoplasmic inclusions in a number of neurodegene rative diseases, including Alzheimer's disease and hereditary frontotempora l dementia and parkinsonism Linked to chromosome 17 (FTDP-17). Over 10 exon ic and intronic mutations in the tau gene have been identified in about 20 FTDP-17 families. Analyses of soluble and insoluble tau proteins from brain s of FTDP-17 patients indicated that different pathogenic mutations differe ntially altered distinct biochemical properties and stoichiometry of brain tau isoforms, Functional assays of recombinant tau proteins with different FTDP-17 missense mutations implicated all but one of these mutations in dis ease pathogenesis by reducing the ability of tau to bind microtubules and p romote microtubule assembly.