Sleep-disordered breathing is associated with Blood-brain barrier markers across the Alzheimer’s disease spectrum

Sleep-disordered breathing (SDB) is prevalent among older adults and is increasingly recognized as a modifiable risk factor for cognitive decline and Alzheimer’s disease (AD). Blood-brain barrier (BBB) dysfunction is an early and mechanistically relevant feature of AD pathophysiology, yet clinical evidence linking SDB to BBB disruption remains limited. We investigated whether SDB is associated with cerebrospinal fluid (CSF) markers of BBB integrity in a well-characterized cohort spanning the AD clinical spectrum. We analyzed cross-sectional data from 409 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). SDB status was ascertained by systematic text-mining of medical history records; 124 participants were classified as SDB-positive (SDB+) and 285 as SDB-negative (SDB−). CSF concentrations of four BBB-related markers PDGFRβ, MMP10, CCL26, and CD40 were compared between groups using multiple linear regression, adjusting for age, sex, BMI, APOE ε4 status, and diagnostic category. Core AD biomarkers (CSF Aβ42 and phosphorylated tau at threonine 181 [p-tau181]) were examined as secondary outcomes. False discovery rate (FDR) correction was applied. SDB+ participants were more frequently male (68.5% vs. 48.1%, p < 0.001) and had higher BMI (29.6 ± 4.5 vs. 26.2 ± 3.9 kg/m², p < 0.001); age and MMSE scores did not differ significantly. After covariate adjustment, SDB was significantly associated with elevated CSF levels of all four BBB markers. An interaction between SDB and APOE ε4 status was significant for PDGFRβ ( p = 0.038), indicating that pericyte-related BBB stress was most pronounced in APOE ε4 carriers with SDB. SDB was also associated with higher CSF p-tau (β ≈ 0.26, p = 0.038) and an elevated p-tau/Aβ ratio (β ≈ 0.17, p = 0.041), though the association with Aβ alone did not reach significance after adjustment (β ≈ −0.05, p = 0.19). PDGFRβ modestly amplified the SDB–p-tau relationship (interaction β ≈ 0.08, p = 0.049). SDB defined by clinical history is associated with a CSF biomarker profile consistent with BBB dysregulation, particularly pericyte injury and vascular inflammation, and with subtle shifts toward greater AD pathological burden. These findings support BBB dysfunction as a plausible mechanistic link between SDB and AD and underscore the need for longitudinal studies examining whether SDB treatment attenuates BBB-related neurodegeneration.