Recent studies suggest that tau hyperphosphorylation may play a dual role in AD neurodegeneration, i.e., tau hyperphosphorylation renders the cells more resistant to acute apoptosis [8–12], while the increasing intracellular tau accumulation induces multiple cellular impairments, including endoplasmic reticulum (ER) stress, deficits of mitophagy and autophagy, deficits of synaptic transmission, etc., and eventually leads to a chronic neurodegeneration [5, 13, 14]. This evidence concerns the gene MAPT and Alzheimer disease.