MAPT and Alzheimer disease: Sleep deprivation exaggerated this wake-related increase, similar to its effects on Aβ, and chronic sleep deprivation increased the spread of tau pathology from the hippocampus to the locus coeruleus in the brainstem (Holth et al., 2019), a norepinephrine-expressing brain region known to accumulate tau pathology in the earliest stages of AD (Grudzien et al., 2007; Braak et al., 2011; Ehrenberg et al., 2017).