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阻塞性睡眠呼吸暂停患者海马体和脑干的阿尔茨海默病神经病理学。

Alzheimer's disease neuropathology in the hippocampus and brainstem of people with obstructive sleep apnea.

机构信息

School of Health and Biomedical Sciences, RMIT University, Bundoora, Victoria, Australia.

Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

出版信息

Sleep. 2021 Mar 12;44(3). doi: 10.1093/sleep/zsaa195.

Abstract

Obstructive sleep apnea (OSA) involves intermittent cessations of breathing during sleep. People with OSA can experience memory deficits and have reduced hippocampal volume; these features are also characteristic of Alzheimer's disease (AD), where they are accompanied by neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques in the hippocampus and brainstem. We have recently shown reduced hippocampal volume to be related to OSA severity, and although OSA may be a risk factor for AD, the hippocampus and brainstems of clinically verified OSA cases have not yet been examined for NFTs and Aβ plaques. The present study used quantitative immunohistochemistry to investigate postmortem hippocampi of 34 people with OSA (18 females, 16 males; mean age 67 years) and brainstems of 24 people with OSA for the presence of NFTs and Aβ plaques. OSA severity was a significant predictor of Aβ plaque burden in the hippocampus after controlling for age, sex, body mass index (BMI), and continuous positive airway pressure (CPAP) use. OSA severity also predicted NFT burden in the hippocampus, but not after controlling for age. Although 71% of brainstems contained NFTs and 21% contained Aβ plaques, their burdens were not correlated with OSA severity. These results indicate that OSA accounts for some of the "cognitively normal" individuals who have been found to have substantial Aβ burdens, and are currently considered to be at a prodromal stage of AD.

摘要

阻塞性睡眠呼吸暂停(OSA)涉及睡眠期间呼吸的间歇性停止。患有 OSA 的人可能会出现记忆缺陷,并伴有海马体体积减小;这些特征也是阿尔茨海默病(AD)的特征,AD 患者的海马体和脑干中还存在神经原纤维缠结(NFT)和淀粉样β(Aβ)斑块。我们最近发现,海马体体积减小与 OSA 的严重程度有关,尽管 OSA 可能是 AD 的一个风险因素,但尚未对经临床验证的 OSA 病例的海马体和脑干进行 NFT 和 Aβ 斑块的检查。本研究使用定量免疫组织化学方法,对 34 名 OSA 患者(18 名女性,16 名男性;平均年龄 67 岁)的海马体和 24 名 OSA 患者的脑干进行了 NFT 和 Aβ 斑块的检测。在控制年龄、性别、体重指数(BMI)和持续气道正压通气(CPAP)使用的情况下,OSA 严重程度是预测海马体 Aβ 斑块负担的一个重要指标。OSA 严重程度也可以预测海马体中的 NFT 负担,但在控制年龄后则不能预测。尽管 71%的脑干存在 NFT,21%的脑干存在 Aβ 斑块,但它们的负担与 OSA 严重程度无关。这些结果表明,OSA 解释了一些“认知正常”的个体,这些个体已经被发现有大量的 Aβ 负担,目前被认为处于 AD 的前驱阶段。

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