Liguori Claudio
Sleep Medicine Centre, Neurophysiopathology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy.
Curr Top Behav Neurosci. 2017;33:305-322. doi: 10.1007/7854_2016_50.
Alzheimer's disease (AD) is the most frequent age-related dementia. It prevalently causes cognitive decline, although it is frequently associated with secondary behavioral disturbances. AD neurodegeneration characteristically produces a remarkable destruction of the sleep-wake cycle, with diurnal napping, nighttime arousals, sleep fragmentation, and REM sleep impairment. It was recently hypothesized that the orexinergic system was involved in AD pathology. Accordingly, recent papers showed the association between orexinergic neurotransmission dysfunction, sleep impairment, and cognitive decline in AD. Orexin is a hypothalamic neurotransmitter which physiologically produces wakefulness and reduces REM sleep and may alter the sleep-wake cycle in AD patients. Furthermore, the orexinergic system seems to interact with CSF AD biomarkers, such as beta-amyloid and tau proteins. Beta-amyloid accumulation is the main hallmark of AD pathology, while tau proteins mark brain neuronal injury due to AD pathology. Investigations so far suggest that orexinergic signaling overexpression alters the sleep-wake cycle and secondarily induces beta-amyloid accumulation and tau-mediated neurodegeneration. Therefore, considering that orexinergic system dysregulation impairs sleep-wake rhythms and may influence AD pathology, it is hypothesized that orexin receptor antagonists are likely potential preventive/therapeutic options in AD patients.
阿尔茨海默病（AD）是最常见的与年龄相关的痴呆症。它主要导致认知能力下降，尽管它经常与继发性行为障碍有关。AD神经退行性变的特征是对睡眠-觉醒周期造成显著破坏，表现为日间小睡、夜间觉醒、睡眠片段化和快速眼动（REM）睡眠障碍。最近有假说认为，食欲素能系统参与了AD的病理过程。相应地，最近的论文表明食欲素能神经传递功能障碍、睡眠障碍与AD患者的认知能力下降之间存在关联。食欲素是一种下丘脑神经递质，在生理上可产生清醒状态并减少REM睡眠，可能会改变AD患者的睡眠-觉醒周期。此外，食欲素能系统似乎与脑脊液中的AD生物标志物相互作用，如β-淀粉样蛋白和tau蛋白。β-淀粉样蛋白的积累是AD病理的主要标志，而tau蛋白则标志着AD病理导致的脑神经元损伤。目前的研究表明，食欲素能信号过度表达会改变睡眠-觉醒周期，并继而诱导β-淀粉样蛋白的积累和tau介导的神经退行性变。因此，考虑到食欲素能系统失调会损害睡眠-觉醒节律并可能影响AD病理，有假说认为食欲素受体拮抗剂可能是AD患者潜在的预防/治疗选择。
