MAPT and Alzheimer disease: From the neuropathological point of view, the brains of AD sufferers are characterized by the presence of two major hallmarks mainly located in the hippocampus and cortex: extracellular amyloid plaques composed of insoluble aggregates of the amyloid-β protein (Aβ) and intraneuronal neurofibrillary tangles, composed of hyperphosphorylated Tau protein (Kosik et al., 1986).