MAPT and Alzheimer disease: The major neuropathological features of AD are intracellular neurofibrillary tangles (NFTs) formed by hyperphosphorylated tau protein, extracellular senile plaques composed of aggregated β-amyloid (Aβ) fibers (Tabaton et al., 1991; Smith, 1998), and progressive brain atrophy causing by loss of synapses and neurons (Butterfield and Halliwell, 2019; Alzheimer’s Association, 2021).