Interaction of obstructive sleep apnea severity and amyloid burden on novel plasma biomarkers of tau and neurofilament light protein in community‐dwelling cognitively normal older‐adults

Abstract

AbstractBackgroundRecent evidence suggest that plasma Tau and neurofilament light (NfL) have high potential as markers of neurodegeneration in Alzheimer disease (AD). Obstructive sleep apnea (OSA) severity increases AD risk and is associated with well‐validated markers of AD pathology in cognitively normal older‐adults. We determined the independent and combined effects of OSA severity and amyloid burden on plasma levels of Tau, and NfL, in community‐dwelling cognitively normal older‐adults.MethodCross‐sectional analysis of baseline data from 70 community‐dwelling cognitively normal older‐adults, selected from ongoing NYU prospective longitudinal studies on memory, sleep and aging. CSF‐Aβ42 (measured using ELISA) quantified amyloid burden. OSA severity was defined using AHI4%. Levels of plasma Tau and NfL were determined using single molecule array (SIMOA) technology ultra‐sensitive assays. Associations of OSA severity and plasma Tau and NfL were assessed using Pearson correlation analysis. The interactive associations of OSA severity and CSF‐Aβ42 levels on plasma Tau and NfL was assessed using generalized linear models. Analyses were adjusted for age, sex, BMI, education and APOE4.ResultOf the 70 participants, 42 (60%) were women. Mean (SD) age was 68.7 (7.1) years. Mean (SD) AHI was 11.4/hr. (13.7) {29 (40%) had AHI <5, 20 (25%) had AHI: 5 to ≤ 15, 11 had AHI: 15 to ≤30 and 10 had AHI >30}. Independent of CSF‐Aβ42, OSA severity was not associated with plasma Tau (r=.11, p‐value=.38), or plasma NfL (r=.05, p‐value=.67). The interactive associations of OSA severity and CSF‐Aβ42 levels on plasma Tau (β =0.042; 95% CI, 0.013 to 0.070) and NfL (β = 0.055; 95% CI, 0.022 to 0.089) were significant, P < .05 for all. The analysis was not powered for generating dichotomized strata specific (i.e. OSA+/Aβ+, OSA+/Aβ‐, OSA‐/Aβ+ and OSA‐/Aβ‐) estimates.ConclusionIn this sample of cognitively normal older‐adults, OSA severity was not associated with plasma levels of Tau and NfL. However, β estimates of the interactive associations of OSA severity and CSF‐Aβ42 levels suggest that their combined effect is associated with higher plasma levels of Tau or NfL. Larger cohorts are necessary to delineate mechanisms and examine for OSA/Aβ strata‐specific estimates.