MAPT and Alzheimer disease: According to the Aβ cascade hypothesis, the increase of Aβ can further induce the hyperphosphorylation of the microtubule-associated protein tau and accumulation in the cells, forming AD-related pathological changes such as neurofibrillary tangles, and leading to increased levels of t-tau and p-tau in the CSF of AD patients (Huang and Mucke, 2012).