Histological studies indicate locus coeruleus (LC) - the brain’s major noradrenergic hub (Nikolenko et al., 2024) - as a first site of tau accumulation in AD, showing pretangle tau in LC before neurofibrillary tangles appear in entorhinal/perirhinal cortices (Braak and Del Tredici, 2011; Weinshenker, 2018). This evidence concerns the gene MAPT and Alzheimer disease.