In large postmortem samples, the burden of hyperphosphorylated tau in the LC significantly increases alongside signficant decreases in LC volume at the earliest stage of AD pathology (Ehrenberg et al., 2017; Theofilas et al., 2017) which may lead to the propogation of tau pathology into noradrenergic projecting cortical regions. Here, MAPT is linked to Alzheimer disease.