MAPT and Alzheimer disease: AD is pathologically characterized by two hallmarks: extracellular senile plaques (SPs) formed by amyloid-β (Aβ) deposited in the extracellular space, and neurofibrillary tangles caused by the aggregation of intracellular hyperphosphorylated tau proteins (Karran et al., 2011; Knopman et al., 2021).