The tau mutation (val337met) disrupts cytoskeletal networks of microtubules

THE missense point mutation found in the tau gene, which was segregated in a family with frontotemporal dementia with parkinsonism; linked to chromoso me 17 (FTDP-17), has proved to be the causal molecule for widely spread dem entia diseases. Here we examined the effects of the tau mutation using conf ocal analysis. When wild-type tau cDNA was introduced into cells, extensive cell processes and well-developed thick bundles of microtubules were induc ed. On the other hand, when altered tau cDNA with the mutation (valine337-m ethionine) was introduced, cell lost processes and microtubule networks res ulted in more round cell shape but showed intact mitochondria or endoplasmi c reticulum. We conclude that the tau mutation primarily affects the microt ubules and resultantly causes the loss of cellular organization and functio n due to microtubule disruption. NeuroReport 10:993-997 (C) 1999 Lippincott Williams & Wilkins.