急性睡眠缺失降低阿尔茨海默病生物标志物的脑脊液到血液清除率。
Acute sleep loss decreases CSF-to-blood clearance of Alzheimer's disease biomarkers.
机构信息
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
Tracy Family SILQ Center, Washington University School of Medicine, St. Louis, Missouri, USA.
出版信息
Alzheimers Dement. 2023 Jul;19(7):3055-3064. doi: 10.1002/alz.12930. Epub 2023 Jan 25.
INTRODUCTION
Sleep deprivation increases cerebrospinal fluid (CSF) amyloid beta (Aβ) and tau levels; however, sleep's effect on Aβ and tau in plasma is unknown.
METHODS
In a cross-over design, CSF Aβ and tau concentrations were measured in five cognitively normal individuals who had blood and CSF collected every 2 hours for 36 hours during sleep-deprived and normal sleep control conditions.
RESULTS
Aβ40, Aβ42, unphosphorylated tau threonine181 (T181), unphosphorylated tau threonine-217 (T217), and phosphorylated T181 (pT181) concentrations increased ∼35% to 55% in CSF and decreased ∼5% to 15% in plasma during sleep deprivation. CSF/plasma ratios of all Alzheimer's disease (AD) biomarkers increased during sleep deprivation while the CSF/plasma albumin ratio, a measure of blood-CSF barrier permeability, decreased. CSF and plasma Aβ42/40, pT181/T181, and pT181/Aβ42 ratios were stable longitudinally in both groups.
DISCUSSION
These findings show that sleep loss alters some plasma AD biomarkers by lowering brain clearance mechanisms and needs to be taken into account when interpreting individual plasma AD biomarkers but not ratios.
简介
睡眠剥夺会增加脑脊液（CSF）中的淀粉样蛋白β（Aβ）和tau 水平；然而，睡眠对血浆中 Aβ和 tau 的影响尚不清楚。
方法
在一项交叉设计中，我们测量了五名认知正常个体的 CSF Aβ 和 tau 浓度，这些个体在睡眠剥夺和正常睡眠对照条件下，每隔 2 小时采集一次血液和 CSF，共 36 小时。
结果
在睡眠剥夺期间，CSF 中 Aβ40、Aβ42、未磷酸化 tau 苏氨酸 181（T181）、未磷酸化 tau 苏氨酸 217（T217）和磷酸化 T181（pT181）浓度增加了约 35%至 55%，而血浆中浓度降低了约 5%至 15%。所有阿尔茨海默病（AD）生物标志物的 CSF/血浆比值在睡眠剥夺期间增加，而 CSF/血浆白蛋白比值（衡量血脑屏障通透性的指标）降低。CSF 和血浆 Aβ42/40、pT181/T181 和 pT181/Aβ42 比值在两组中均保持稳定。
讨论
这些发现表明，睡眠不足通过降低大脑清除机制来改变一些血浆 AD 生物标志物，在解释个体血浆 AD 生物标志物时需要考虑这一点，但比值则不需要。
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