Alzheimer's disease; Human aging; Locus coeruleus; Norepinephrine; Sleep microstructure; Sleep-wake regulation; Tau pathology; Aging; Humans; Sleep/physiology; Alzheimer Disease; Locus Coeruleus/physiology; Sleep; Pulmonary and Respiratory Medicine; Neurology; Neurology (clinical); Physiology (medical)
Abstract :
[en] 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.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Van Egroo, Maxime ✱; Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, the Netherlands.
Vandewalle, Gilles ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Jacobs, Heidi I L ; Faculty of Health, Medicine and Life Sciences, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht University, Maastricht, the Netherlands, Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
✱ These authors have contributed equally to this work.
Language :
English
Title :
Importance of the locus coeruleus-norepinephrine system in sleep-wake regulation: Implications for aging and Alzheimer's disease.
ULiège - Université de Liège [BE] WBI - Wallonie-Bruxelles International [BE] Fondation Recherche Alzheimer [BE] NIA - National Institute on Aging [US-MD] [US-MD] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE] BrightFocus Foundation [US-MD] [US-MD]
Funding text :
M.V.E. is supported by Wallonia-Brussels International ( SOR /2020/479197 ) and BrightFocus Foundation ( A20211016F ). E.K. and G.V. are supported by Fonds De La Recherche Scientifique - FNRS Belgium (F.R.S.-FNRS, F.4513.17 & T.0242.19 ), Fondation Recherche Alzheimer ( SAO-FRA 2019/0025 ), and University of Liège . H.I.L.J. receives funding from the National Institute on Aging ( R01AG062559 , R01AG068062 , R21AG074220 ). Practice Points Research Agenda
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