Importance of the locus coeruleus-norepinephrine system in sleep-wake regulation: Implications for aging and Alzheimer's disease. (April 2022)

• Record Type: Journal Article
• Authors: Van Egroo, Maxime; Koshmanova, Ekaterina; Vandewalle, Gilles; Jacobs, Heidi I.L.
• Is Part Of: Sleep medicine reviews. Volume 62(2022)
• Publication Date: 2022-04
• Subjects: Locus coeruleus -- Norepinephrine -- Sleep-wake regulation -- Sleep microstructure -- Human aging -- Tau pathology -- Alzheimer's disease; Sleep disorders -- Periodicals; Sleep Disorders -- Periodicals; Sommeil, Troubles du -- Périodiques; Electronic journals; 616.8498
• DOI: 10.1016/j.smrv.2022.101592
• Languages: English
• ISSNs: 1087-0792

Abstract

Summary: 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.