Therefore, we propose the following network: Orexin signaling influences hippocampal oscillation; simultaneously, the hippocampal oscillator controls the circadian expression of AD-risk genes like Bace1, Bace2, and ApoE, which are key genes in Aβ metabolism; the rhythmicity of these AD-risk genes indicates that AD is associated with circadian oscillation; finally, orexin signaling is involved in the reciprocal control of the core clock feedback loop and AD (Fig. 7). The gene discussed is APOE; the disease is Alzheimer disease.