MAPT and Alzheimer disease: β-amyloid deposit and hyperphosphorylated tau protein hypothesis: AD is originated from the presence of extraneuronal amyloid plaques formed by amyloid fibers composed of Aβ protein, and intraneuronal neurofibrillary tangles (NFTs), that are mainly formed by paired helical filaments (PHF) of the hyperphosphorylated tau protein (Gallardo and Holtzman, 2019; Paroni et al., 2019; Arnsten et al., 2021).