Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, the Netherlands.
Sleep and Chronobiology Lab, GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium.
Sleep Med Rev. 2022 Apr;62:101592. doi: 10.1016/j.smrv.2022.101592. Epub 2022 Jan 21.
Five decades ago, seminal studies positioned the brainstem locus coeruleus (LC) norepinephrine (NE) system as a key substrate for the regulation of wakefulness and sleep, and this picture has recently been elaborated thanks to methodological advances in the precise investigation and experimental modulation of LC structure and functions. This review presents and discusses findings that support the major role of the LC-NE system at different levels of sleep-wake organization, ranging from its involvement in the overall architecture of the sleep-wake cycle to its associations with sleep microstructure, while accounting for the intricate neuroanatomy surrounding the LC. Given the particular position held by the LC-NE system by being at the intersection of sleep-wake dysregulation and initial pathophysiological processes of Alzheimer's disease (AD), we conclude by examining emerging opportunities to investigate LC-NE mediated relationships between sleep-wake alteration and AD in human aging. We further propose several research perspectives that could support the LC-NE system as a promising target for the identification of at-risk individuals in the preclinical stages of AD, and for the development of novel preventive interventions.
五十年前，开创性的研究将脑桥蓝斑（LC）去甲肾上腺素（NE）系统定位为调节觉醒和睡眠的关键基质，而最近由于在精确研究和实验调节 LC 结构和功能方面的方法学进展，这一图景得到了进一步的阐述。本综述介绍并讨论了支持 LC-NE 系统在睡眠-觉醒组织不同水平上发挥主要作用的发现，范围从其参与睡眠-觉醒周期的整体结构到与睡眠微结构的关联，同时考虑到 LC 周围复杂的神经解剖结构。鉴于 LC-NE 系统在睡眠-觉醒失调和阿尔茨海默病（AD）初始病理生理过程的交叉点上的特殊位置，我们最后通过检查研究 LC-NE 介导的睡眠-觉醒改变与人类衰老中 AD 之间关系的新机会来得出结论。我们进一步提出了几个研究视角，这些视角可以支持 LC-NE 系统作为识别 AD 临床前阶段高危个体和开发新的预防干预措施的有前途的目标。
