Tau is the most abundant microtubule associated protein. The normal function of Tau is to promote microtubule assembly and stabilize microtubules. In Alzheimer's disease, Tau is abnormally hyperphosphorylated and the hyperphosphorylated Tau accumulates, in the form of paired helical filaments (PHF), in the neuron to form neurofibrillary tangles. Numerous studies indicate that the abnormal Tau modifications play a crucial role in AD neurodegeneration and the cognitive deficits. We have studied systemically the mechanisms underlie Tau hyperphosphorylation and the effects of Tau phosphorylation on cell viability. We found unexpectedly that expression of the hyperphosphorylated Tau, at certain point, renders the cells more resistant to the exogenously induced cell apoptosis, whereas dephosphorylation of Tau promotes cell apoptosis. We also found that persistent Tau hyperphosphorylation and the cellular accumulation damage the neural functions and thus decrease the viability. Based on these findings, we propose that Tau hyperphosphorylation may play a dual role in leading the neurons to abort from an acute apoptosis and at the same time triggering a chronic neurodegeneration, which may explain why the degenerated neurons observed in the postmortem Alzheimer's brain are enriched with the hyperphosphorylated Tau proteins/tangles. It is suggested that proper intervention of Tau hyperphosphorylation may serve as a promising strategy in rescuing cell apoptosis and arresting neurodegeneration in Alzheimer's disease.