GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Liège, Belgium.
Psychology and Cognitive Neuroscience Research Unit, University of Liège, Liège, Belgium.
Sleep. 2019 Apr 1;42(4). doi: 10.1093/sleep/zsz017.
While efficient treatments for Alzheimer's disease (AD) remain elusive, a growing body of research has highlighted sleep-wake regulation as a potential modifiable factor to delay disease progression. Evidence accumulated in recent years is pointing toward a tight link between sleep-wake disruption and the three main hallmarks of the pathogenesis of AD, i.e. abnormal amyloid-beta (Aβ) and tau proteins accumulation, and neurodegeneration. However, all three hallmarks are rarely considered together in the same study. In this review, we gather and discuss findings in favor of an association between sleep-wake disruption and each AD hallmark in animal models and in humans, with a focus on the preclinical stages of the disease. We emphasize that these relationships are likely bidirectional for each of these hallmarks. Altogether, current findings provide strong support for considering sleep-wake disruption as a true risk factor in the early unfolding of AD, but more research integrating recent technical advances is needed, particularly with respect to tau protein and neurodegeneration. Interventional longitudinal studies among cognitively healthy older individuals should assess the practical use of improving sleep-wake regulation to slow down the progression of AD pathogenesis.
虽然治疗阿尔茨海默病（AD）的有效方法仍难以捉摸，但越来越多的研究强调睡眠-觉醒调节是一种潜在的可改变因素，可以延缓疾病的进展。近年来积累的证据表明，睡眠-觉醒中断与 AD 发病机制的三个主要特征之间存在紧密联系，即异常淀粉样蛋白-β（Aβ）和 tau 蛋白积累以及神经退行性变。然而，所有这三个特征很少在同一研究中同时考虑。在这篇综述中，我们汇集并讨论了支持在动物模型和人类中睡眠-觉醒中断与 AD 每个标志之间存在关联的发现，重点关注疾病的临床前阶段。我们强调，对于这些特征中的每一个，这些关系都可能是双向的。总之，目前的研究结果为将睡眠-觉醒中断视为 AD 早期发生的真正风险因素提供了有力支持，但需要更多整合最新技术进展的研究，特别是关于 tau 蛋白和神经退行性变。在认知健康的老年人中进行干预性纵向研究，应评估改善睡眠-觉醒调节以减缓 AD 发病机制进展的实际用途。
