McConnell Brice V, Deng Yulin, Lucey Brendan P
Department of Neurology, University of Colorado School of Medicine, Aurora, CO.
University of Colorado Alzheimer's and Cognition Center, Aurora, CO.
Curr Sleep Med Rep. 2025 Dec;11(1). doi: 10.1007/s40675-024-00316-6. Epub 2025 Jan 3.
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.
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.
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.
本综述旨在概述介导睡眠与神经退行性疾病（如阿尔茨海默病）之间双向关系的潜在机制。我们提供了先前提出的机制的最新信息，并确定了新的机制，特别是关于睡眠障碍如何影响与记忆相关的神经回路。
在本综述中，我们重点关注可能介导睡眠与阿尔茨海默病之间关系的多种机制。我们介绍了先前假设机制的最新情况，如淀粉样β蛋白和tau蛋白产生/释放及清除过程中与睡眠相关的变化，以及最近提出的与tau磷酸化、食欲素系统、星形胶质细胞和小胶质细胞相关的机制。我们还强调了在阿尔茨海默病中，作为与记忆相关神经回路基础的睡眠脑电图振荡（如慢波活动、θ爆发、睡眠纺锤波和γ波）的破坏情况。
睡眠障碍通过多种潜在机制增加患阿尔茨海默病的风险，这表明有多个靶点可用于测试已批准的、有效的睡眠障碍治疗方法，以预防或延缓阿尔茨海默病。
