MAPT and Alzheimer disease: The hypothesis has evolved over the past 25 years to basically suggest that deposition of Aβ in brain parenchyma as a downstream result of aberrant cleavage of its precursor protein, APP, either due to mutations in APP or due to mutations in AD-associated presenilin genes, PSEN1 and 2, leads to neurofibrillary tangles via tau and, ultimately, neuronal death [140].