Body rhythms may shape Abeta clearance through the in Alzheimer's disease-relevant biology.
Evidence
Systematic review links cardiovascular, respiratory, neural, circadian, and exercise rhythms to glymphatic Abeta clearance mechanisms and proposed interventions for AD.
Caveat
The paper provides a mechanistic theoretical basis for synchronized multi-rhythm interventions, not clinical outcome evidence that these approaches prevent or treat AD.
Simplified
Abnormal deposition of β-amyloid (Aβ) is a significant pathological feature of neurodegenerative diseases, particularly Alzheimer's disease (AD). The (GS) plays a crucial role in Aβ clearance. Various rhythmic activities of the organism dynamically influence Aβ clearance by modulating GS function. In this paper, we systematically review the mechanisms linking cardiovascular rhythms, respiratory rhythms, neural rhythms, circadian rhythms, and exercise patterns to Aβ clearance via the GS. Cardiovascular rhythms affect cerebral perfusion pressure and vascular pulsation to regulate GS transport efficiency; respiratory rhythms modulate intracranial pressure and cerebrospinal fluid (CSF) circulation through thoracic pressure variations; neural rhythms (including delta waves during non-rapid eye movement (NREM) sleep and neurovascular coupling) synchronize neuro-glial-vascular interactions to enhance GS clearance. Circadian rhythms coordinate these primary rhythms by regulating melatonin levels and cerebral blood flow, while exercise patterns adjust GS function via aquaporin-4 (AQP4) polarization. Additionally, we elaborate on the cascade effect of AD resulting from rhythmic dysregulation. A thorough understanding of how rhythmic activities impact Aβ clearance by the GS may offer new perspectives and potential intervention strategies for the prevention and treatment of AD through the concept of "synchronized multiple rhythms"-a novel framework that integrates multi-rhythm synergy. Clinically, this work provides a theoretical basis for developing targeted interventions, such as personalized exercise timing regimens, respiratory rhythm training, and closed-loop neurovascular feedback devices, to restore GS function in AD patients.
Key numbers
65%
Decrease in Aβ clearance
Reduction in Aβ clearance after cardiac arrest within 1 hour.
35%
Increase in AQP4 polarization
AQP4 polarization increase due to δ-waves during NREM sleep.
40%
Decrease in Alzheimer's risk
Reduction in AD risk associated with maintaining cardiorespiratory fitness.
Full Text
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