Sleep Architecture and Serum Biomarker Heterogeneity in Obstructive Sleep Apnea: A Cross-Sectional Study

Abstract Study Objectives To determine whether sleep architecture is associated with heterogeneity in serum biomarkers of neuronal injury, astroglial stress, tau-related pathology, and neuroplasticity in adults with obstructive sleep apnea (OSA). Methods Adults referred for suspected OSA underwent overnight polysomnography and next-morning fasting serum sampling. Primary analyses were restricted to participants with OSA (apnea-hypopnea index > = 5 events/h; n = 82). Serum NSE, NfL, BDNF, CREB1, S100B, GFAP, and p-Tau/human pMAPT/pTAU were measured by ELISA. We first examined whole-group correlations between respiratory burden (AHI, ODI, and T90) and biomarkers, then fit age- and sex-adjusted linear models with continuous sleep-stage percentages. Median-split stage analyses and stage-stratified correlations were treated as exploratory sensitivity analyses. Results Biomarker availability ranged from 70 to 71 participants. Lower REM percentage was independently associated with higher ln(NSE) (beta = -0.0138 per 1% REM; 95% CI, -0.026 to -0.001; p=.033). Whole-group BDNF correlated inversely with ODI (rho = -0.299, p=.011) and AHI (rho = -0.277, p=.020). In sensitivity analyses, REM-AHI was positively associated with p-Tau/human pMAPT/pTAU (beta = 1.799, p=.006) and GFAP (beta = 2.094, p=.024). Interaction terms testing formal effect modification by REM% or N3% were directionally consistent with the hypothesis but did not reach conventional significance. After Bonferroni correction, only the short-REM AHI-BDNF correlation remained significant among exploratory stage-stratified correlations. Conclusions Reduced REM sleep showed the clearest and most reproducible relationship with an adverse peripheral biomarker profile in OSA, specifically higher serum NSE. Sleep architecture may contribute to biomarker heterogeneity, but evidence for stage-dependent modification of hypoxemia-biomarker relationships remains exploratory.