MAPT and Alzheimer disease: The main pathological changes observed in AD include the accumulation of Aβ to form senile plaques (SPs), the formation of intracellular neurofibrillary tangles (NFTs) caused by the abnormal deposition of excessive tau phosphorylation, and gliosis with neuronal loss [33], while impairment of the protein clearance pathway contributes to abnormal protein deposition.