Combined genetic, biomarker and histopathological data indicate increasing Aβ peptide concentrations as driving force for the conversion from preclinical to mild cognitive impairment (MCI) and finally AD [19, 25, 26, 53], strongly correlating with spreading of Tau-pathology beyond EC and the limbic system to the neocortex, by a poorly understood molecular mechanism. Here, MAPT is linked to Alzheimer disease.