Furthermore, while HCRT may not be necessary for sleep loss-induced amyloid plaque in AD transgenic mice, HCRT may play a role in other early pathologic manifestations in AD, for example loss of cholinergic fibers in the hippocampus (Stokin et al., 2005), which may contribute to impaired cognition in AD (Hampel et al., 2018). This evidence concerns the gene HCRT and Alzheimer disease.