Moreover, post-mortem studies performed in patients with AD documented a reduction in orexinergic neurons and significantly lower CSF orexin-A levels compared to controls [19, 34], suggesting that the in vivo documentation of high CSF orexin-A levels may reflect the modification of orexinergic neurotransmission depending on factors such as sleep-wake cycle dysregulation, feeding, and behavior more than the integrity of the orexin system [3, 35–37]. This evidence concerns the gene HCRT and Alzheimer disease.