LAUSR

Recent evidence suggests novel plasma Alzheimer’s Disease (AD) pathology biomarkers have high potential for AD risk prediction. We determined whether obstructive sleep apnea (OSA) severity is associated with plasma levels of Aβ40, Aβ42, Aβ42/Aβ40, Tau, tau/Aβ42 and NfL and whether this relationship is dependent of amyloid burden. Cross-sectional analysis of baseline data from 120 community-dwelling, cognitively normal older-adults, selected from ongoing NYU prospective longitudinal studies on memory, sleep and aging. Of the 120 participants, 70 had baseline CSF-Aβ42 (measured using ELISA). OSA-severity was defined using AHI4% criteria. Levels of plasma Aβ40, Aβ42, Tau and NfL were determined using single molecule array technology ultra-sensitive assays. Associations of OSA-severity and plasma AD-biomarker levels (n=120) were assessed using Pearson correlation analysis. The association of OSA-severity and AD plasma biomarkers dependent on CSF-Aβ42 levels (n=70) was assessed using generalized linear models. Analyses were adjusted for age, sex, BMI, race, education and APOE4. Of the 120 participants, 80 (67%) were women. Mean (SD) age was 69.1 (7.2) years. Mean (SD) AHI was 14.3/hr. (16.3) {48 (40%) had AHI <5, 30 (25%) had AHI: 5 to ≤ 15, 18 (15%) had AHI: 15 to ≤30, and 22 (18%) had AHI >30}. Independent of amyloid-burden, OSA-severity was associated with higher levels of plasma Aβ40 (r=.21, p-value=.02), plasma Aβ42 (r=.26, p-value=.01), plasma Aβ42/Aβ40 (r=.20, p-value=.05), but not plasma Tau, plasma tau/Aβ42 or plasma NfL. The association of OSA-severity and plasma levels of Tau, Tau/Aβ42 or NfL dependent on CSF-Aβ42 levels revealed significant interactions between CSF-Aβ42 levels and AHI (p-value <.05 for all), with β-estimates suggesting that with combined increases in AHI and decreases in CSF-Aβ42 levels, there were corresponding increases in plasma levels of Tau, plasma Tau/Aβ42 or plasma NfL. The analysis was not powered for generating dichotomized strata specific (i.e. OSA+/Aβ+, OSA+/Aβ-, OSA-/Aβ+ and OSA-/Aβ-) estimates. In this sample of cognitively-normal older- adults, OSA-severity was associated with levels of plasma Aβ40, Aβ42, Aβ42/Aβ40 and showed a synergistic effect with CSF Aβ42 on plasma levels of tau and NfL. Larger cohorts are necessary to delineate mechanisms and examine for OSA/Aβ strata-specific estimates. NIH/NIA/NHLBI (L30-AG064670, CIRAD-P30AG059303-Pilot, NYU-ADRC-P30AG066512-Developmental-Grant, AASM#231-BS-20)