MAPT and Alzheimer disease: Although a complex disease, two well-defined phenomena are recognized in AD: the amyloid-related neuropathological alterations in the brain, due to accumulation and deposition of amyloid-β (Aβ) peptide [157] derived from proteolysis of Aβ precursor protein (APP) [158], and the tau-related neuropathological alterations which results in intracellular insoluble neurofibrillary tangles [159].