Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease?

• Published in: Trends in neurosciences (Regular ed.) Vol. 39; no. 8; pp. 552 - 566
• Main Authors: Mander, Bryce A., Winer, Joseph R., Jagust, William J., Walker, Matthew P.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2016; Elsevier Sequoia S.A; Elsevier - Cell Press
• Subjects: aging; Aging - physiology; Alzheimer Disease - diagnosis; Alzheimer Disease - physiopathology; Alzheimer Disease - therapy; Alzheimer's disease; amyloid-β; Animals; BASIC BIOLOGICAL SCIENCES; Brain; cognitive decline; Eye movements; Humans; Medical treatment; Memory; Neurology; Neurosciences; Sleep; Sleep - drug effects; Sleep - physiology; sleep; amyloid-β; aging; cognitive decline; Alzheimer's disease
• ISSN: 0166-2236; 1878-108X; 1878-108X
• DOI: 10.1016/j.tins.2016.05.002

Sleep disruption appears to be a core component of Alzheimer's disease (AD) and its pathophysiology. Signature abnormalities of sleep emerge before clinical onset of AD. Moreover, insufficient sleep facilitates accumulation of amyloid-β (Aβ), potentially triggering earlier cognitive decline and conversion to AD. Building on such findings, this review has four goals: evaluating (i) associations and plausible mechanisms linking non-rapid-eye-movement (NREM) sleep disruption, Aβ, and AD; (ii) a role for NREM sleep disruption as a novel factor linking cortical Aβ to impaired hippocampus-dependent memory consolidation; (iii) the potential diagnostic utility of NREM sleep disruption as a new biomarker of AD; and (iv) the possibility of sleep as a new treatment target in aging, affording preventative and therapeutic benefits. A bidirectional, causal interaction exists between NREM sleep and Aβ pathophysiology that may contribute to Alzheimer's disease (AD) risk and progression. The disruption of NREM sleep may represent a novel pathway through which cortical Aβ impairs hippocampus-dependent memory consolidation. The disruption of NREM sleep physiology offers potential diagnostic utility in the form of a non-invasive biomarker of Aβ pathology, AD risk, and/or AD pathophysiological progression. Evidence implicates sleep disturbance as a consequence and cause of AD progression; one that is modifiable, offering preventative and therapeutic treatment potential.