MAPT and Alzheimer disease: Although the two classical hallmarks, extracellular senile plaques (SPs) aggregated by amyloid beta-peptide (Aβ) around the neurons and intraneuronal neurofibrillary tangles (NFTs) embodying hyperphosphorylated tau protein (p-tau), were confirmed for AD decades ago (Kosik et al., 1986; Yamada et al., 1988), the neuropathogenesis of AD has not been fully elucidated.