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MINI-REVIEW

The mind awake at night: Glymphatic dysfunction as a mechanistic bridge linking multifactorial sleep disturbances to neurodegeneration

Josué Camberos-Barraza1 ,  Karyme M. Alemán-Villa1 ,  Alberto K. De la Herrán-Arita1*
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1 Department of Neurosciences, School of Medicine, Autonomous University of Sinaloa, Culiacán, Sinaloa, México
JCBP, 025390076 https://doi.org/10.36922/JCBP025390076
Received: 26 September 2025 | Revised: 7 November 2025 | Accepted: 26 November 2025 | Published online: 9 December 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Chronic sleep disorders are a major modifiable risk factor for neurodegenerative diseases. However, the mechanisms linking the diverse etiologies of sleep disorders to neuropathology are not fully understood. This review synthesizes evidence to position glymphatic system dysfunction as a critical “mechanistic bridge” linking the multifactorial drivers of disordered sleep, ranging from psychophysiological hyperarousal to intermittent hypoxia and circadian misalignment, to the pathogenesis of neurodegeneration. The brain’s glymphatic system is essential for clearing neurotoxins, such as amyloid-β and α-synuclein, a process that is most efficient during deep, non-rapid eye movement sleep. This review outlines how distinct sleep-disrupting conditions, despite their different origins, converge on a final common pathway: The failure to establish the low-noradrenergic state required for effective glymphatic clearance. This suppression provides a direct mechanism linking poor sleep to the accumulation of toxic proteins that are hallmarks of neurodegenerative diseases. We also explore the evidence for a bidirectional, self-perpetuating cycle, where initial protein accumulation can, in turn, damage sleep-regulating brain nuclei, further degrading sleep and accelerating pathology. This framework reframes the management of all sleep disorders, not merely as symptom control, but as a tangible strategy for neuroprotection.

Keywords
Glymphatic system
Sleep apnea
Insomnia
Neurodegeneration
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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Journal of Clinical and Basic Psychosomatics, Electronic ISSN: 2972-4414 Print ISSN: 3060-8562, Published by AccScience Publishing
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