Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments

Missense mutations and intronic mutations in the gene for microtubule-assoc iated protein tan cause frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), Most missense mutations have as likely primary eff ect a reduced ability of tau to interact with microtubules, We report here an additional effect of several missense mutations, namely the stimulation of heparin-induced filament assembly of recombinant tan. despite the absenc e of any change in structure indicated by circular dichroism. These finding s indicate that missense mutations in tau lead to frontotemparal dementia t hrough potentially multiple mechanisms. (C) 1999 Federation of European Bio chemical Societies.