CLOCK and Alzheimer disease: There are also suggestive results reinforcing the evidence that AD pathology leads to increased wakefulness and high sleep fragmentation in transgenic mouse models (Roh et al., 2012) and results in neuronal loss of the suprachiasmatic nucleus (SCN), the master circadian clock of mammals, and the locus coeruleus, which are essential for maintaining normal wakefulness (Wang et al., 2015).