MAPT and Alzheimer disease: There are two main pathological hallmarks of AD: (1) the presence of increased extracellular Aβ plaques, formed due to the aggregation and impaired clearance of Aβ oligomers (hydrophobic Aβ aggregates) [25,26], and (2) the formation of NFTs [27] that are composed of an insoluble intracellular hyperphosphorylated microtubule-associated protein tau [28,29,30,31,32,33,34,35,36,37,38].