神经源性血浆外泌体中改变的淀粉样蛋白-β和tau 蛋白与阻塞性睡眠呼吸暂停有关。

Altered amyloid-β and tau proteins in neural-derived plasma exosomes in obstructive sleep apnea.

机构信息

Department of Neurology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China.

Department of Pathology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, China.

出版信息

Sleep Med. 2022 Jun;94:76-83. doi: 10.1016/j.sleep.2022.03.021. Epub 2022 Apr 1.

DOI:10.1016/j.sleep.2022.03.021

PMID:35504110

Abstract

OBJECTIVE

The purpose of our study was to investigate the correlation between neural-derived plasma exosomal amyloid-β (Aβ)42, total tau (T-tau) and tau phosphorylated at threonine 181 (P-T181-tau) protein levels and cognitive impairment in patients with obstructive sleep apnea (OSA).

METHODS

There were 122 subjects without dementia included in the study: 27 patients with OSA and mild cognitive impairment (MCI), 52 OSA patients without MCI, and 43 subjects diagnosed with simple snoring but not MCI as the control group. Neuronal-derived exosomal proteins were measured by ELISA kits for Aβ42, T-tau and P-T181-tau. The cognitive function was evaluated by a Chinese version of the Montreal Cognitive Assessment (MoCA) questionnaire, and a normal cognitive score was ≥26.

RESULTS

The exosomal Aβ42, T-tau and P-T181-tau levels in the OSA with MCI group were higher than those in the OSA group. The Aβ42, T-tau, and P-T181-tau levels in the plasma neuronal-derived exosomes were associated with an increased risk of cognitive impairment in OSA patients after additional adjustment for age, gender, education, vascular risk factors, apnea-hypopnea index (AHI) or oxygen reduction index (ODI). Furthermore, there were also significant associations between Aβ42, T-tau, and P-T181-tau in neural-derived plasma exosomes and Epworth Sleepiness Scale, AHI, and ODI in OSA patients. After 1 year of continuous positive airway pressure (CPAP) intervention, the neuronal-derived exosome levels of Aβ42, T-tau, and P-T181-tau were significantly lower than those at baseline (P = 0.001, P = 0.012, and P = 0.034).

CONCLUSIONS

These findings indicate that peripheral blood levels of neuronal-derived exosomal Aβ and tau proteins were increased in OSA patients with cognitive impairment. CPAP interventions could possibly improve cognitive function and be associated with decreased levels of exosomal Aβ and tau proteins.

摘要

目的

本研究旨在探讨阻塞性睡眠呼吸暂停（OSA）患者神经源性血浆外泌体淀粉样蛋白β（Aβ）42、总tau（T-tau）和 tau 磷酸化在苏氨酸 181 位（P-T181-tau）蛋白水平与认知障碍的相关性。

方法

本研究共纳入 122 例无痴呆患者：27 例 OSA 合并轻度认知障碍（MCI）患者、52 例 OSA 无 MCI 患者和 43 例单纯鼾症但无脑 MCI 患者作为对照组。采用 ELISA 试剂盒检测神经元衍生外泌体蛋白 Aβ42、T-tau 和 P-T181-tau。采用中文版蒙特利尔认知评估（MoCA）问卷评估认知功能，正常认知评分≥26 分。

结果

OSA 合并 MCI 组的外泌体 Aβ42、T-tau 和 P-T181-tau 水平高于 OSA 组。在校正年龄、性别、教育程度、血管危险因素、呼吸暂停低通气指数（AHI）或氧减指数（ODI）后，血浆神经元衍生外泌体中的 Aβ42、T-tau 和 P-T181-tau 水平与 OSA 患者认知障碍风险增加相关。此外，OSA 患者中 Aβ42、T-tau 和 P-T181-tau 与 Epworth 嗜睡量表、AHI 和 ODI 之间也存在显著相关性。经过 1 年持续气道正压通气（CPAP）干预后，神经元衍生外泌体 Aβ42、T-tau 和 P-T181-tau 水平均较基线时显著降低（P=0.001、P=0.012 和 P=0.034）。