MAPT and Alzheimer disease: Along with a decline in cognitive performance, AD is characterized by the coexistence in the brain of two main neuropathological lesions: intraneuronal neurofibrillary tangles composed of hyperphosphorylated microtubule-associated protein tau and extracellular senile plaques containing the amyloid-β (Aβ) peptide generated from the sequential proteolytic processing of its precursor, the amyloid precursor protein (APP).