MAPT and Alzheimer disease: In line with tau distribution patterns in sporadic AD (Braak and Braak, 1991), autopsy investigations of DS have found tau pathology to affect the entorhinal cortex first, then the hippocampus as well as the locus coeruleus and dorsal raphe nucleus, eventually reaching the neocortical areas in the fifth decade (Davidson et al., 2018; Mann et al., 1986).