Neurofibrillary tangles (NFTs) are regarded as one of the major pathological features of Alzheimer's disease, and are composed of misfolded and aggreagted Tau protein with hyperphosphorylation. But the mechanism of Tau hyperphosphorylation still remains to be clarified. This review summarized the roles of endogenous and exogenous factors in the induction of Tau hyperphosphorylation. The level of some factors and the hyperphosphorylation of Tau could be used as biomarkers for the early processing of AD.