Tau proteins with FTDP-17 mutations have a reduced ability to promote microtubule assembly.

Recently exonic and intronic mutations in the gene for microtubule-associated protein tau have been discovered in cases of familial frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). Intronic mutations have been shown to lead to an abnormal preponderance of four-repeat tau isoforms. The effects of the exonic mutations are unknown. We report here that the G272V, P301L, V337M and R406W mutations lead to a marked reduction in the ability of tau to promote microtubule assembly. This partial loss-of-function may be the primary effect of the known missense mutations in tau.