MAPT and Alzheimer disease: Central pathologic events in AD are as follows: (i) the abnormal cleavage of amyloid precursor protein (APP), resulting in the accumulation of Aβ plaques in the extracellular space, and (ii) the hyperphosphorylation of microtubule-associated protein tau, leading to the formation of intracellular neurofibrillary tangles (NFTs).