Local Sleep and Alzheimer's Disease Pathophysiology.
Local Sleep and Alzheimer's Disease Pathophysiology.
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局部睡眠和阿尔茨海默病病理生理学。
DOI：
10.3389/fnins.2020.525970
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发表时间：
2020
影响因子：
4.3
通讯作者：
Mander BA
中科院分区：
文献类型：
--
作者：
Mander BA
甚至在阿尔茨海默病（AD）的前驱期发作之前，一系列睡眠障碍是明显的。一系列流行病学研究表明，这些睡眠障碍的多种形式与轻度认知障碍（MCI）和AD的风险增加有关，甚至在较早的年龄引发疾病发作。通过结合人类和啮齿动物的因果操纵研究，以及针对AD生物标志物的睡眠障碍的靶向检查，将睡眠障碍与AD联系起来的机制开始出现。在这篇综述中，我们探讨了最近的证据表明，在睡眠中的局部脑振荡功能的缺陷与局部AD病理负担和电路水平的功能障碍和退化。简而言之，已经确定了与AD病理生理学相关的睡眠振荡局部表达的三种缺陷：（1）非快速眼动（NREM）睡眠期间慢波表达的频率特异性额叶缺陷，（2）顶叶睡眠纺锤体表达的缺陷，以及（3）REM睡眠特征性脑电图（EEG）质量的缺陷。这些缺陷是值得注意的，因为它们不同于正常老化中所见的缺陷，表明可能存在异常老化过程。这些都是如何与β-淀粉样蛋白（Aβ）和tau病理，以及神经退行性病变的电路敏感的AD病理生理学，在本审查中检查，重点是功能障碍的作用额海马和皮层下睡眠-觉醒电路。据推测，这些局部睡眠缺陷中的每一个都是由AD病理的区域特异性积累以及其相关的神经变性驱动的独特的网络特异性功能障碍引起的。总的来说，这些局部睡眠不足的演变提供了独特的窗口到电路特定的进展，不同的AD病理生理过程之前，AD发作，以及它们对脑功能的影响。这包括睡眠依赖性记忆机制的潜在侵蚀，这可能导致AD的记忆下降。本文最后讨论了剩余的关键知识差距和这项工作对未来机制研究和实施基于睡眠的治疗干预措施的研究的影响。
Even prior to the onset of the prodromal stages of Alzheimer’s disease (AD), a constellation of sleep disturbances are apparent. A series of epidemiological studies indicate that multiple forms of these sleep disturbances are associated with increased risk for developing mild cognitive impairment (MCI) and AD, even triggering disease onset at an earlier age. Through the combination of causal manipulation studies in humans and rodents, as well as targeted examination of sleep disturbance with respect to AD biomarkers, mechanisms linking sleep disturbance to AD are beginning to emerge. In this review, we explore recent evidence linking local deficits in brain oscillatory function during sleep with local AD pathological burden and circuit-level dysfunction and degeneration. In short, three deficits in the local expression of sleep oscillations have been identified in relation to AD pathophysiology: (1) frequency-specific frontal deficits in slow wave expression during non-rapid eye movement (NREM) sleep, (2) deficits in parietal sleep spindle expression, and (3) deficits in the quality of electroencephalographic (EEG) desynchrony characteristic of REM sleep. These deficits are noteworthy since they differ from that seen in normal aging, indicating the potential presence of an abnormal aging process. How each of these are associated with β-amyloid (Aβ) and tau pathology, as well as neurodegeneration of circuits sensitive to AD pathophysiology, are examined in the present review, with a focus on the role of dysfunction within fronto-hippocampal and subcortical sleep-wake circuits. It is hypothesized that each of these local sleep deficits arise from distinct network-specific dysfunctions driven by regionally-specific accumulation of AD pathologies, as well as their associated neurodegeneration. Overall, the evolution of these local sleep deficits offer unique windows into the circuit-specific progression of distinct AD pathophysiological processes prior to AD onset, as well as their impact on brain function. This includes the potential erosion of sleep-dependent memory mechanisms, which may contribute to memory decline in AD. This review closes with a discussion of the remaining critical knowledge gaps and implications of this work for future mechanistic studies and studies implementing sleep-based treatment interventions.
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影响因子：
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