Pro-apoptotic effects of tau mutations in chromosome 17 frontotemporal dementia and parkinsonism

It was recently discovered that mutations of tau cause hereditary frontotem poral dementia and parkinsonism linked to chromosome 17 (FTDP-17). Here we repels that cultured SH-SY5Y human neuroblastoma cells transfected with mut ated tau genes are more vulnerable to apoptotic stimulus. Two kinds of muta tions of tau causing FTDP-17 were examined in the present study: one was in exon 10 (N279K) and the other was in exon 12 (V337M). SH-SY5Y cells transf ected with either mutated tau were more vulnerable to serum withdrawal, whe reas cells transfected with the wild-type tau or vector alone showed no sig nificant change in apoptotic vulnerability. The increase in the intracellul ar calcium concentration by the serum withdrawal was significantly greater in the SH-SY5Y cells transfected with mutated tau genes than in cells trans fected with the wild-type tau or vector alone. These results suggest that m utations of tau might cause FTDP-17 by these proapoptotic functions by disr upting the intracellular calcium homeostasis. NeuroReport 11:57-60 (C) 2000 Lippincott Williams & Wilkins.