Sleep and Neurodegeneration: Examining Potential Physiological Mechanisms

Brice V. McConnell, Yulin Deng, Brendan P. Lucey

Research output: Contribution to journalReview articlepeer-review

Abstract

Purpose of the Review: The purpose of this review is to provide an overview of potential mechanisms mediating the bi-directional relationship between sleep and neurodegenerative diseases such as Alzheimer’s disease. We provide updates on previously proposed mechanisms and identify new mechanisms particularly concerning how sleep disturbances affect memory-related neural circuits. Recent Findings: In this review, we focus on the multiple mechanisms that potentially mediate the relationship between sleep and Alzheimer’s disease. We present updates for previously hypothesized mechanisms such as sleep-related changes in production/release and clearance of amyloid-β and tau proteins as well as more recently proposed mechanisms relating to tau phosphorylation, the orexin system, astrocytes, and microglia. We also highlight how disruptions in sleep EEG oscillations that underlie memory-related neural circuits, such as slow wave activity, theta bursts, sleep spindles, and gamma ripples, change in Alzheimer’s disease. Summary: Disturbed sleep increases Alzheimer’s disease risk via multiple potential mechanisms that suggest multiple targets to test approved and effective treatments of sleep disorders to prevent or delay Alzheimer’s disease.

Original languageEnglish
Article number1
JournalCurrent Sleep Medicine Reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2025

Keywords

  • Alzheimer’s disease
  • Amyloid-beta
  • Neural circuits
  • Sleep
  • Slow wave activity
  • Tau

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