This observation led some researchers to suggest that a primary tauopathy unrelated to AD exists as a benign age-related entity that might affect all humans if they live long enough [32] (Fig. 3b) and that the clinical diagnosis of AD can only and exclusively be confirmed by the accelerated accumulation of both p-tau and amyloid in the cortex and neocortex. This evidence concerns the gene MAPT and Alzheimer disease.