Associations between obstructive sleep apnea and Alzheimer's disease-related biomarkers (amyloid-β and tau) in blood and cerebrospinal fluid: a systematic review and meta-analysis

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% C I [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.