MAPT and Alzheimer disease: Through analyzing its activity, researchers found that cyclic levels of orexin during normal rhythmic activity were inversely proportional to tau protein aggregation; high Aβ plaque aggregation and tau protein pathology also result in disturbances in non-REM sleep activity, ascertaining the bidirectional influence of circadian rhythmicity and AD pathology (Kilduff et al., 2008; Kang et al., 2009; Liu et al., 2019).