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Sleep oscillation-specific associations with Alzheimer's disease CSF biomarkers: novel roles for sleep spindles and tau.
Molecular Neurodegeneration ( IF 15.1 ) Pub Date : 2019-02-21 , DOI: 10.1186/s13024-019-0309-5
Korey Kam 1 , Ankit Parekh 1 , Ram A Sharma 2 , Andreia Andrade 2 , Monica Lewin 3 , Bresne Castillo 1 , Omonigho M Bubu 2 , Nicholas J Chua 1 , Margo D Miller 2 , Anna E Mullins 1 , Lidia Glodzik 2 , Lisa Mosconi 4 , Nadia Gosselin 5 , Kulkarni Prathamesh 2 , Zhe Chen 2 , Kaj Blennow 6, 7 , Henrik Zetterberg 6, 7, 8, 9 , Nisha Bagchi 1 , Bianca Cavedoni 2 , David M Rapoport 1 , Indu Ayappa 1 , Mony J de Leon 3 , Eva Petkova 2, 10 , Andrew W Varga 1 , Ricardo S Osorio 2, 3
Affiliation  

BACKGROUND Based on associations between sleep spindles, cognition, and sleep-dependent memory processing, here we evaluated potential relationships between levels of CSF Aβ42, P-tau, and T-tau with sleep spindle density and other biophysical properties of sleep spindles in a sample of cognitively normal elderly individuals. METHODS One-night in-lab nocturnal polysomnography (NPSG) and morning to early afternoon CSF collection were performed to measure CSF Aβ42, P-tau and T-tau. Seven days of actigraphy were collected to assess habitual total sleep time. RESULTS Spindle density during NREM stage 2 (N2) sleep was negatively correlated with CSF Aβ42, P-tau and T-tau. From the three, CSF T-tau was the most significantly associated with spindle density, after adjusting for age, sex and ApoE4. Spindle duration, count and fast spindle density were also negatively correlated with T-tau levels. Sleep duration and other measures of sleep quality were not correlated with spindle characteristics and did not modify the associations between sleep spindle characteristics and the CSF biomarkers of AD. CONCLUSIONS Reduced spindles during N2 sleep may represent an early dysfunction related to tau, possibly reflecting axonal damage or altered neuronal tau secretion, rendering it a potentially novel biomarker for early neuronal dysfunction. Given their putative role in memory consolidation and neuroplasticity, sleep spindles may represent a mechanism by which tau impairs memory consolidation, as well as a possible target for therapeutic interventions in cognitive decline.

中文翻译:

睡眠振荡与阿尔茨海默氏病脑脊液生物标志物的特定关联:睡眠纺锤体和tau的新作用。

背景技术基于睡眠纺锤,认知和依赖睡眠的记忆处理之间的关联,我们在此评估了样本中CSFAβ42,P-tau和T-tau水平与睡眠纺锤密度和其他睡眠纺锤生物物理特性之间的潜在关系。认知正常的老年人。方法进行一夜的实验室夜间多导睡眠监测(NPSG)和从早至下午的CSF收集,以测量CSFAβ42,P-tau和T-tau。收集了七天的书法,以评估习惯性的总睡眠时间。结果NREM 2期(N2)睡眠期间的纺锤体密度与CSFAβ42,P-tau和T-tau呈负相关。在对年龄,性别和ApoE4进行校正后,三者中CSF​​ T-tau与纺锤体密度最相关。主轴持续时间 计数和快速纺锤体密度也与T-tau水平呈负相关。睡眠时间和其他睡眠质量指标与纺锤体特征无关,也没有改变睡眠纺锤体特征与AD的CSF生物标志物之间的关联。结论N2睡眠期间纺锤体减少可能代表与tau有关的早期功能障碍,可能反映了轴突损伤或神经元tau分泌改变,使其成为早期神经元功能障碍的潜在新生物标志物。考虑到它们在记忆巩固和神经可塑性中的推定作用,睡眠纺锤体可能代表tau损害记忆巩固的机制,以及认知障碍治疗干预的可能目标。睡眠时间和其他睡眠质量指标与纺锤体特征无关,也没有改变睡眠纺锤体特征与AD的CSF生物标志物之间的关联。结论N2睡眠期间纺锤体减少可能代表与tau有关的早期功能障碍,可能反映了轴突损伤或神经元tau分泌改变,使其成为早期神经元功能障碍的潜在新生物标志物。考虑到它们在记忆巩固和神经可塑性中的推定作用,睡眠纺锤体可能代表tau损害记忆巩固的机制,以及认知障碍治疗干预的可能目标。睡眠时间和其他睡眠质量指标与纺锤体特征无关,也没有改变睡眠纺锤体特征与AD的CSF生物标志物之间的关联。结论N2睡眠期间纺锤体减少可能代表与tau有关的早期功能障碍,可能反映了轴突损伤或神经元tau分泌改变,使其成为早期神经元功能障碍的潜在新生物标志物。考虑到它们在记忆巩固和神经可塑性中的推定作用,睡眠纺锤体可能代表tau损害记忆巩固的机制,以及认知障碍治疗干预的可能目标。结论N2睡眠期间纺锤体减少可能代表与tau有关的早期功能障碍,可能反映了轴突损伤或神经元tau分泌改变,使其成为早期神经元功能障碍的潜在新生物标志物。考虑到它们在记忆巩固和神经可塑性中的推定作用,睡眠纺锤体可能代表tau损害记忆巩固的机制,以及认知障碍治疗干预的可能目标。结论N2睡眠期间纺锤体减少可能代表与tau有关的早期功能障碍,可能反映了轴突损伤或神经元tau分泌改变,使其成为早期神经元功能障碍的潜在新生物标志物。考虑到它们在记忆巩固和神经可塑性中的推定作用,睡眠纺锤体可能代表tau损害记忆巩固的机制,以及认知障碍治疗干预的可能目标。
更新日期:2019-02-21
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