Letter to the editor regarding "Biomarkers of Alzheimer's disease in severe obstructive sleep apnea-hypopnea syndrome in the Chinese population"
Letter to the editor regarding "Biomarkers of Alzheimer's disease in severe obstructive sleep apnea-hypopnea syndrome in the Chinese population"
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关于“中国人群严重阻塞性睡眠呼吸暂停低通气综合征中阿尔茨海默病的生物标志物”致编辑的信
DOI：
10.1007/s00405-021-06968-2
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kawada T
中科院分区：
文献类型：
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作者：
Sato Chiaki;Sato Hiroki;Kamei Takashi;Shimamura Yuto;Tanaka Shinwa;Shiwaku Hironari;Shiota Junya;Ogawa Ryo;Yokomichi Hiroshi;Inoue Haruhiro;Kawada T
我读了孔令辉等人发表的题为《严重阻塞性睡眠呼吸暂停低通气综合征中阿尔茨海默病的生物标记物》的文章。怀着极大的兴趣。探讨阻塞性睡眠呼吸暂停低通气综合征(OSAS)患者阿尔茨海默病生物标志物水平，重度OSAS患者血浆Aβ40、总tau(t-tau)和磷酸化tau(p-tau)水平均显著高于对照组。此外，Aβ42、Aβ40、t-tau和p-tau与阻塞性睡眠呼吸暂停综合征指标、简易精神状态检查量表得分和Epworth嗜睡量表得分显著相关。OSAS患者的认知功能下降可能存在于这一人群中，这可能是反复夜间低氧的部分原因。日间嗜睡增加应通过对OSAS的适当治疗来改善，这将导致防止认知障碍的进展。我对他们的学习有些担心。首先，作者没有引用Bu等人的参考文献，后者研究了阻塞性睡眠呼吸暂停综合征患者慢性间歇性低氧与Aβ之间的关系[2]。阻塞性睡眠呼吸暂停综合征患者血清A-β-40、A-β-42和总A-β水平均显著高于对照组。此外，这些生物标志物与呼吸暂停低通气指数、氧减饱和指数以及平均和最低氧合血红蛋白饱和度呈正相关。此外，OSAS患者血清p-tau 181水平显著升高。他们推测，慢性间歇性低氧和A-β水平升高可能与阿尔茨海默病的发病机制有关。他们测量的是血清样本，而不是血浆样本，而且样本数量有限。我认为，可能需要进行干预研究，以证实阻塞性睡眠呼吸暂停综合征与随后的认知损害和阿尔茨海默病风险之间的因果关系。其次，作者还引用了Bubu等人的一篇综述，他们总结了研究OSA和认知障碍/阿尔茨海默病的报告，包括生物标记物。持续气道正压治疗对改善认知功能可能是有效的，而且在任何一代人中，OSAS与神经退行性变的生物标志物之间都存在联系。不幸的是，通过调整许多混杂因素和相互作用，缺乏关于剂量-反应关系的足够信息，包括OSAS的严重程度和持续时间以及随后的认知损害和阿尔茨海默病的风险。需要进一步的研究才能进行高质量的荟萃分析。最后，Nakamura等人。报道称，基于血液的淀粉样蛋白-β生物标记物的临床应用尚未确定[4]。这意味着，淀粉样蛋白-β正电子发射断层扫描成像或脑脊液中淀粉样蛋白-β的测量与基于血液的淀粉样蛋白-β生物标志物的一致性并不令人满意。他们开发了一种新的免疫沉淀与质谱学相结合的系统，用于测量高性能血浆淀粉样蛋白-β生物标记物。Aβ-β前体蛋白(APP)669-711/A-β(A-β)1-42和A-β1-40/A-β1-42比值及其复合体用于通过A-β-β显像预测个体脑内淀粉样蛋白-PET状态。通过受试者-操作特征曲线分析，该复合生物标志物表现出较高的预测能力，并且这些生物标志物与脑淀粉样蛋白-β-正电子发射体层摄影负荷和脑脊液中A-β1-42水平显著相关。尽管许多用于测量的测量工具
I read the article titled “Biomarkers of Alzheimer’s disease in severe obstructive sleep apnea–hypopnea syndrome in the Chinese population” by Kong et al. with great interest [1]. The authors explored the level of Alzheimer’s disease biomarkers in patients with obstructive sleep apnea–hypopnea syndrome (OSAS), and the mean plasma levels of Aβ40, total tau (t-tau), and phosphorylated tau (p-tau) in patients with severe OSAS were significantly higher than those in the control group. In addition, Aβ42, Aβ40, t-tau, and p-tau were significantly associated with indicators of OSAS, Mini-Mental State examination scale scores, and Epworth Sleepiness Scale scores. Cognitive decline in patients with OSAS may be existed in this population, which could be partly explained by repeated night hypoxia. Increased daytime sleepiness should be improved by appropriate treatment for OSAS, which would lead to prevent progression of cognitive impairment. I have some concerns about their study. First, the authors did not cite a reference by Bu et al., which examined the association between the chronic intermittent hypoxia and Aβ in OSAS patients [2]. The mean serum levels of Aβ40, Aβ42, and total Aβ levels in patients with OSAS were significantly higher than those in the control group. In addition, these biomarkers were positively associated with the apnea–hypopnea index, the oxygen desaturation index, and the mean and lowest oxyhemoglobin saturations. Furthermore, the OSAS patients exhibited a significant increase of serum p-tau 181 levels. They speculated that chronic intermittent hypoxia and increased Aβ levels would contribute to the pathogenesis of Alzheimer’s disease. They measured serum, not plasma, samples and the number of samples was limited. I think that intervention study may be needed to verify a causal relationship of OSAS and subsequent risk of cognitive impairment and Alzheimer’s disease. Second, the authors also cited a review by Bubu et al., who summarized reports examining OSA and cognitive impairment/Alzheimer’s disease, including biomarkers. Continuous positive airway pressure treatment for OSAS may be effective in improving cognition, and there is a link between OSAS and biomarkers of neurodegeneration in any generation. Unfortunately, there is a lack of enough information regarding dose–response relationship including severity and duration of OSAS and subsequent risk of cognitive impairment and Alzheimer’s disease by adjusting many confounders and interactions. Further studies are required for conducting a high-quality meta-analysis. Finally, Nakamura et al. reported that the clinical use of blood-based amyloid-β biomarkers has not been established [4]. This means that the agreement of amyloid-β positronemission tomography (PET) imaging or measurement of amyloid-β in cerebrospinal fluid with blood-based amyloid-β biomarkers is not satisfactory. They developed a new system of immunoprecipitation coupled with mass spectrometry for the measurement of high-performance plasma amyloid-β biomarkers. The ability of amyloid-β precursor protein (APP) 669–711/amyloid-β (Aβ) 1–42 and Aβ1-40/Aβ1-42 ratios, and their composites were used to predict individual brain amyloid-β status by amyloid-β-PET imaging. The composite biomarker showed high performance of predictive ability by receiver-operating characteristics curve analysis, and these biomarkers were significantly correlated with brain amyloid-β-PET burden and levels of Aβ1-42 in cerebrospinal fluid. Although many measurement kits for