MAPT and Alzheimer disease: There are two major hallmarks of AD as follows; (1) development of amyloidal plaques outside the cells nerve due to cleavage of membrane-embedded proteins (amyloid precursor proteins: APP) into the neurotoxic single amyloidal units (amyloid-beta: Aβ) peptides during proteolytic processing by secretases enzymes, such as β and γ-secretase, and (2) formation of neurofibrillary tangles (NFTs) inside the nerve cells due to accumulation of paired helical filaments of hyperphosphorylated tau proteins [6].