Gérontopôle AURA, 42000 Saint-Etienne, France.
Inserm, U1059, Sainbiose, Faculté de Médecine Jacques Lisfranc, Université de Lyon, 42000 Saint-Etienne, France.
Int J Mol Sci. 2024 Oct 15;25(20):11058. doi: 10.3390/ijms252011058.
Obstructive sleep apnea syndrome (OSAS) affects a large part of the aging population. It is characterized by chronic intermittent hypoxia and associated with neurocognitive dysfunction. One hypothesis is that the blood-brain barrier (BBB) functions could be altered by exosomes. Exosomes are nanovesicles found in biological fluids. Through the study of exosomes and their content in tau and amyloid beta (Aβ), the aim of this study was to show how exosomes could be used as biomarkers of OSAS and of their cognitive disorders. Two groups of 15 volunteers from the PROOF cohort were selected: severe apnea (AHI > 30) and control (AHI < 5). After exosome isolation from blood serum, we characterized and quantified them (CD81, CD9, CD63) by western blot and ELISAs and put them 5 h in contact with an in vitro BBB model. The apparent permeability of the BBB was measured using sodium-fluorescein and TEER. Cell ELISAs were performed on tight junctions (ZO-1, claudin-5, occludin). The amount of tau and Aβ proteins found in the exosomes was quantified using ELISAs. Compared to controls, OSAS patients had a greater quantity of exosomes, tau, and Aβ proteins in their blood sera, which induced an increase in BBB permeability in the model and was reflected by a loss of tight junction' expression. Elderly patients suffering severe OSAS released more exosomes in serum from the brain compartment than controls. Such exosomes increased BBB permeability. The impact of such alterations on the risk of developing cognitive dysfunction and/or neurodegenerative diseases is questioned.
阻塞性睡眠呼吸暂停综合征（OSAS）影响了很大一部分老年人群。其特征为慢性间歇性缺氧，并与神经认知功能障碍相关。有一个假设是，血脑屏障（BBB）的功能可能会被外泌体改变。外泌体是在生物体液中发现的纳米囊泡。通过研究外泌体及其在tau 和淀粉样蛋白 β（Aβ）中的含量，本研究旨在展示外泌体如何可作为 OSAS 及其认知障碍的生物标志物。从 PROOF 队列中选择了两组各 15 名志愿者：严重呼吸暂停（AHI > 30）和对照组（AHI < 5）。从血清中分离出外泌体后，我们通过 Western blot 和 ELISA 对其进行了特征和定量（CD81、CD9、CD63），并将其与体外 BBB 模型接触 5 小时。通过荧光素钠和 TEER 测量 BBB 的表观渗透率。在紧密连接（ZO-1、claudin-5、occludin）上进行细胞 ELISA。使用 ELISA 定量在外泌体中发现的 tau 和 Aβ 蛋白的量。与对照组相比，OSAS 患者的血清中外泌体、tau 和 Aβ 蛋白的含量更多，这导致模型中 BBB 通透性增加，并反映在紧密连接表达的丧失上。患有严重 OSAS 的老年患者从大脑隔室释放到血清中的外泌体比对照组更多。这种外泌体增加了 BBB 的通透性。这些改变对发展认知功能障碍和/或神经退行性疾病的风险的影响受到质疑。
