In AD, tau pathology first arises in the brainstem nuclei projecting broadly to the cerebral cortex (e.g., noradrenergic locus coeruleus) and in the cerebral cortex emerges in the transentorhinal region (TRE) and then in superficial cellular layers of the entorhinal region (ER) early in the course of the illness inducing degeneration (Braak et al., 2011; Braak and Del Tredici, 2014). This evidence concerns the gene MAPT and Alzheimer disease.