However, the complexity of this relationship must be noted as not only has increased orexinergic signaling been associated with the progression of AD, orexins have been shown to increase amyloid-β in the interstitial fluid (Kang et al., 2009) and there is a documented correlation between tau proteins and orexin CSF levels and sleep-wake dysregulation in AD patients (Liguori et al., 2020b). The gene discussed is HCRT; the disease is Alzheimer disease.