MAPT and Alzheimer disease: AD brain neuropathology is characterized classically by two hallmark lesions: neuritic plaques (NPs, Fig. 1A) constituted by extracellular deposits of the amyloid-β peptide (Aβ), and neurofibrillary tangles (NFTs, Fig. 1B) composed of paired helical filaments (PHFs), whose main constituent is tau protein.