The locus coeruleus is important in AD because studies suggest that this region may be the earliest site of tau pathology, and tau neurofibrillary tangles and volume loss in the locus coeruleus are associated with AD duration and severity (Bondareff et al., 1987; Grudzien et al., 2007; Braak and Del Tredici, 2011). This evidence concerns the gene MAPT and Alzheimer disease.