MAPT and Alzheimer disease: The pathological hallmarks of AD are amyloid plaques and neurofibrillary tangles; amyloid plaques are created by the extracellular deposition of fibrils consisting of abnormally folded Aβ peptide—a cleavage product of amyloid precursor protein (APP)3—while neurofibrillary tangles consist mainly of intracellular hyperphosphorylated twisted filaments of the microtubule-associated Tau protein (Tau hereafter)1,4.