Amyloid-β (Aβ) plaques are a key histopathological hallmark of Alzheimer's disease (AD), and soluble Aβ species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aβ plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aβ homeostasis may be connected in the setting of AD. Aβ, like many interstitial solutes, is cleared in part through the exchange of brain interstitial fluid and cerebrospinal fluid along a brain-wide network of perivascular pathways recently termed the glymphatic system. Glymphatic function is primarily a feature of the sleeping brain, rather than the waking brain, and is slowed in the aging and posttraumatic brain. These changes may underlie the diurnal fluctuations in interstitial and cerebrospinal fluid Aβ levels observed in both the rodent and the human. These and other emerging studies suggest that age-related sleep disruption may be one key factor that renders the aging brain vulnerable to Aβ deposition and the development of AD. If this is true, sleep may represent a key modifiable risk factor or therapeutic target in the preclinical phases of AD.

中文翻译：

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间质液-脑脊液交换、β淀粉样蛋白和睡眠之间的新关系

β 淀粉样蛋白 (Aβ) 斑块是阿尔茨海默病 (AD) 的一个关键组织病理学标志，可溶性 Aβ 种类被认为在该疾病的临床发展中发挥着重要作用。新出现的生物标志物数据表明，Aβ斑块沉积在临床症状出现前几十年就开始了，这表明了解 AD 病理学发展最早步骤的生物决定因素可能为 AD 治疗和预防提供关键机会。尽管睡眠中断与 AD 之间的临床关联早已得到认可，但新兴的临床研究和基础神经科学的见解为了解 AD 背景下睡眠和 Aβ 稳态之间的关系提供了重要的新线索。Aβ 与许多间质溶质一样，部分是通过脑间质液和脑脊液沿全脑血管周围通路网络（最近称为类淋巴系统）的交换而被清除的。类淋巴功能主要是睡眠大脑的特征，而不是清醒大脑的特征，并且在衰老和创伤后大脑中会减慢。这些变化可能是在啮齿动物和人类中观察到的间质和脑脊液 Aβ 水平的昼夜波动的基础。这些和其他新兴研究表明，与年龄相关的睡眠中断可能是导致衰老大脑容易受到 Aβ 沉积和 AD 发展的关键因素。如果这是真的，那么睡眠可能代表 AD 临床前阶段的一个关键的可改变危险因素或治疗目标。