An executive role of Tau in the pathogenetic process of AD and related Tauopathies is substantiated by (i) the existence of a family of neurodegenerative disorders all characterized by Tau-aggregation, by (ii) the identification of MAPT mutations autosomal dominantly linked to these Tauopathies, indicating that Tau dysfunction causes neurodegeneration, and by (iii) the strong correlation of progression of Tau pathology with progression of disease symptoms in AD—generally considered as a secondary Tauopathy [9, 11, 85, 92]. Here, MAPT is linked to Alzheimer disease.