MAPT and Alzheimer disease: In the past decades, neuropathological diagnosis of Alzheimer’s disease (AD) was based on the semiquantitative evaluation of I) extracellular neuritic plaques composed of amyloid-beta (Ab) surrounded by dystrophic neurites and II) on the distribution of neurofibrillary degeneration characterized by phospho-tau (pt) immunoreactive intraneuronal fibrillary deposits, together usually referred to as AD-related lesions.