Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.
J Alzheimers Dis. 2020;75(2):471-482. doi: 10.3233/JAD-191122.
Concentrations of soluble amyloid-β (Aβ) oscillate with the sleep-wake cycle in the interstitial fluid of mice and cerebrospinal fluid (CSF) of humans. Further, the concentration of Aβ in CSF increases during sleep deprivation. Stress and disruption of the circadian clock are additional mechanisms hypothesized to increase CSF Aβ levels. Cortisol is a marker for stress and has an endogenous circadian rhythm. Other factors such as glucose and lactate have been associated with changes in sleep-wake activity and/or Aβ.
In this exploratory study, we used samples collected in a previous study to examine how sleep deprivation affects Aβ, cortisol, lactate, and glucose in plasma and CSF from healthy middle-aged adults (N = 11).
Eleven cognitively normal participants without evidence of sleep disturbance were randomized to sleep deprivation or normal sleep control. All participants were invited to repeat the study. Cortisol, lactate, glucose, and Aβ were measured in 2-h intervals over a 36-h period in both plasma and CSF. All concentrations were normalized to the mean prior to calculating mesor, amplitude, acrophase, and other parameters.
One night of sleep deprivation increases the overnight concentration of Aβ in CSF approximately 10%, but does not significantly affect cortisol, lactate, or glucose concentrations in plasma or CSF between the sleep-deprived and control conditions.
These data suggest that sleep deprivation-related changes in CSF Aβ are not mediated by stress or circadian disruption as measured by cortisol.
可溶性淀粉样蛋白-β（Aβ）在小鼠间质液和人类脑脊液（CSF）中的浓度随睡眠-觉醒周期波动。此外，在睡眠剥夺期间，CSF 中的 Aβ 浓度增加。应激和生物钟紊乱是另外两种被假设可以增加 CSF Aβ 水平的机制。皮质醇是应激的标志物，具有内源性的昼夜节律。其他因素，如葡萄糖和乳酸，与睡眠-觉醒活动和/或 Aβ 的变化有关。
在这项探索性研究中，我们使用之前研究中收集的样本，检查睡眠剥夺如何影响健康中年成年人（N=11）的血浆和 CSF 中的 Aβ、皮质醇、乳酸和葡萄糖。
11 名认知正常且无睡眠障碍证据的参与者被随机分配到睡眠剥夺或正常睡眠对照组。所有参与者均被邀请重复该研究。在 36 小时的时间内，每隔 2 小时测量一次血浆和 CSF 中的皮质醇、乳酸、葡萄糖和 Aβ。在计算中值、幅度、峰相和其他参数之前，将所有浓度标准化为平均值。
一夜的睡眠剥夺会使 CSF 中 Aβ 的 overnight 浓度增加约 10%，但在睡眠剥夺和对照条件下，不会显著影响血浆或 CSF 中的皮质醇、乳酸或葡萄糖浓度。
这些数据表明，睡眠剥夺相关的 CSF Aβ 变化不是由皮质醇测量的应激或昼夜节律紊乱介导的。
