阻塞性睡眠呼吸暂停与血液及脑脊液中阿尔茨海默病相关生物标志物（淀粉样蛋白β和tau）之间的关联：一项系统综述和荟萃分析。

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中文摘要

目的： 本研究旨在通过系统综述和荟萃分析，阐明阻塞性睡眠呼吸暂停（OSA）与血液及脑脊液（CSF）中阿尔茨海默病（AD）相关生物标志物——特别是淀粉样蛋白β（Aβ）和tau蛋白——之间的关系。
方法： 检索了PubMed、Web of Science（WOS）、Embase和Cochrane Library，检索时间从数据库建库至2024年12月30日（PROSPERO注册号：CRD420251148709）。纳入报告OSA患者与非OSA对照者血液或CSF中Aβ40、Aβ42、总Aβ（T-Aβ）、总tau（T-tau）或磷酸化tau（P-tau）水平的研究。所有荟萃分析均采用随机效应模型。使用适当的验证工具评估偏倚风险。
结果： 共纳入13项研究（7项血液研究，6项CSF研究）。在血液中，OSA患者的T-Aβ（SMD = 0.66，95% CI [0.34, 0.97]，I² = 0%，p < 0.01）和T-tau（SMD = 1.48，95% CI [0.33, 2.62]，I² = 93.6%，p = 0.011）显著更高。血液Aβ40、Aβ42、Aβ42/Aβ40比值或P-tau未发现显著差异。在CSF中，OSA患者的Aβ40（SMD = -1.13，95% CI [-1.65, -0.60]，I² = 0%，p < 0.01）和Aβ42（SMD = -1.23，95% CI [-1.84, -0.63]，I² = 77.3%，p < 0.01）显著更低，但Aβ42/Aβ40比值、T-tau或P-tau无差异。
局限性： 高异质性、以横断面设计为主、大多数结局的GRADE证据确定性为低至极低、回顾性注册以及研究数量有限，均妨碍因果推断，需谨慎解读。
结论： 这项探索性荟萃分析揭示了某些AD相关生物标志物与OSA之间存在区室特异性关联。然而，鉴于现有证据的确定性为低至极低，且预测区间频繁跨越无效值所反映出的巨大不确定性，这些发现应被视为产生假设而非结论性证据。值得注意的是，P-tau或CSF Aβ42/Aβ40比值缺乏一致改变，不支持已确立AD神经病理学的直接特征。未来需要严格设计的大规模前瞻性研究，以确定这些生物标志物变化反映的是早期AD病理还是对OSA相关缺氧和睡眠片段化的可逆生理反应。系统综述注册：https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1148709，标识符CRD420251148709。

英文摘要

PURPOSE: This study aimed to clarify the relationship between obstructive sleep apnea (OSA) and Alzheimer's disease (AD)-related biomarkers-specifically amyloid β (Aβ) and tau proteins-in blood and cerebrospinal fluid (CSF) through a systematic review and meta-analysis.
METHODS: PubMed, Web of Science (WOS), Embase, and Cochrane Library were searched from database inception to December 30, 2024 (PROSPERO registration: CRD420251148709). Studies reporting blood or CSF levels of Aβ40, Aβ42, total Aβ (T-Aβ), total tau (T-tau), or phosphorylated tau (P-tau) in patients with OSA vs. non-OSA controls were included. A random-effects model was employed for all meta-analyses. The risk of bias was assessed using appropriate validated tools.
RESULTS: Thirteen studies (seven blood, six CSF) were included. In blood, OSA patients showed significantly higher T-Aβ (SMD = 0.66, 95% CI [0.34, 0.97], I 2 = 0%, p < 0.01) and T-tau (SMD = 1.48, 95% CI [0.33, 2.62], I 2 = 93.6%, p = 0.011). No significant differences were found for blood Aβ40, Aβ42, Aβ42/Aβ40 ratio, or P-tau. In CSF, patients with OSA had significantly lower Aβ40 (SMD = -1.13, 95% CI [-1.65, -0.60], I 2 = 0%, p < 0.01) and Aβ42 (SMD = -1.23, 95% CI [-1.84, -0.63], I 2 = 77.3%, p < 0.01), but no differences in Aβ42/Aβ40 ratio, T-tau, or P-tau.
LIMITATIONS: High heterogeneity, pre-dominantly cross-sectional designs, low-to-very-low GRADE certainty for most outcomes, retrospective registration, and limited study numbers preclude causal inference and warrant cautious interpretation.
CONCLUSIONS: This exploratory meta-analysis revealed compartment-specific associations between certain AD-related biomarkers and OSA. However, given the low-to-very-low certainty of the available evidence and the substantial uncertainty reflected by prediction intervals that frequently crossed the null value, these findings should be regarded as hypothesis-generating rather than conclusive. Notably, the absence of consistent alterations in P-tau or the CSF Aβ42/Aβ40 ratio argues against a direct signature of established AD neuropathology. Future rigorously designed, large-scale prospective studies are warranted to determine whether these biomarker changes reflect early AD pathology or reversible physiological responses to OSA-related hypoxia and sleep fragmentation.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=1148709, identifier CRD420251148709.