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Decrease in sleep depth is associated with higher cerebrospinal fluid neurofilament light levels in Alzheimer’s disease patients
Sleep ( IF 5.3 ) Pub Date : 2020-08-07 , DOI: 10.1093/sleep/zsaa147
Adriano Targa 1, 2 , Faride Dakterzada 3 , Ivan Benítez 1, 2 , Ricard López 3 , Montserrat Pujol 1 , Mireia Dalmases 1, 2 , Alfonso Arias 3 , Manuel Sánchez-de-la-Torre 1, 2 , Henrik Zetterberg 4, 5, 6 , Kaj Blennow 6, 7 , Reinald Pamplona 8 , Mariona Jové 8 , Ferran Barbé 1, 2 , Gerard Piñol-Ripoll 3
Affiliation  

STUDY OBJECTIVES The majority of studies investigating the association between sleep and Alzheimer's disease (AD) biomarkers have been performed in healthy subjects. Our objective was to investigate the association between sleep and several biomarkers that reflect distinct aspects of AD physiopathology. METHODS The cohort included 104 individuals with mild-moderate AD. The subjects were submitted to one-night polysomnography, and cerebrospinal fluid was collected in the following morning to measure the selected biomarkers associated with amyloid deposition, tau pathology, neurodegeneration, axonal damage, synaptic integrity, neuroinflammation, and oxidative damage. RESULTS There was a positive correlation between neurofilament light (NF-L) and the time spent in N1 sleep and a negative correlation between this marker and the time spent in N3 sleep. Accordingly, we observed that deep sleep was associated with lower levels of NF-L, whereas light sleep increased the probability of having higher levels of this marker. Furthermore, chitinase 3-like 1 (YKL-40) was negatively correlated with sleep efficiency, the time spent in N2 sleep and the time spent in N3 sleep. Conversely, there was a positive correlation between N3 sleep and the oxidative protein damage markers N-ε-(carboxyethyl)lysine and N-ε-(malondialdehyde)lysine. CONCLUSIONS There were significant correlations between sleep parameters and AD biomarkers related to axonal damage and neuroinflammation, such as NF-L and YKL-40. A lack of deep sleep was associated with higher levels of NF-L. This highlights a potential role for NF-L as a biomarker of sleep disruption in mild-moderate AD patients in addition to its role in predicting neurodegeneration and cognitive decline.

中文翻译:

阿尔茨海默病患者睡眠深度的减少与脑脊液神经丝光水平较高有关

研究目标 调查睡眠与阿尔茨海默病 (AD) 生物标志物之间关联的大多数研究都是在健康受试者中进行的。我们的目标是调查睡眠与反映 AD 病理生理学不同方面的几种生物标志物之间的关联。方法 该队列包括 104 名轻中度 AD 患者。受试者接受一晚多导睡眠监测,第二天早上收集脑脊液,以测量与淀粉样蛋白沉积、tau 病理学、神经变性、轴突损伤、突触完整性、神经炎症和氧化损伤相关的选定生物标志物。结果 神经丝光 (NF-L) 与 N1 睡眠时间呈正相关,该标记物与 N3 睡眠时间呈负相关。因此,我们观察到深度睡眠与较低水平的 NF-L 相关,而轻度睡眠增加了该标志物水平较高的可能性。此外,几丁质酶 3 样 1 (YKL-40) 与睡眠效率、N2 睡眠时间和 N3 睡眠时间呈负相关。相反,N3 睡眠与氧化蛋白损伤标志物 N-ε-(羧乙基)赖氨酸和 N-ε-(丙二醛)赖氨酸之间呈正相关。结论 睡眠参数与轴突损伤和神经炎症相关的 AD 生物标志物(如 NF-L 和 YKL-40)之间存在显着相关性。缺乏深度睡眠与较高水平的 NF-L 相关。这突出了 NF-L 作为轻度至中度 AD 患者睡眠中断的生物标志物的潜在作用,以及其在预测神经变性和认知能力下降方面的作用。
更新日期:2020-08-07
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