Elevated tau and interleukin-6 concentrations in adults with obstructive sleep apnea

Abstract

Obstructive sleep apnea (OSA) is characterized by apneas and hypopneas that result in hypoxia, cerebral hypoperfusion, endothelial dysfunction, inflammation, and oxidative stress. These pathophysiologic processes likely contribute to neuronal damage. Tau is a protein that stabilizes microtubules and, along with amyloid beta (Aβ), is associated with neurodegenerative processes. We sought to determine if tau and other biomarkers of inflammation were related to OSA severity. Concentrations of tau, Aβ40, Aβ42, c-reactive protein (CRP), TNF-α, interleukin (IL)-6, and IL-10 were measured in blood and compared between participants with moderate-severe OSA (n = 28), those with mild OSA (n = 22), and healthy controls (n = 24). The cohort included relatively young, primarily male active duty military personnel without a history of traumatic brain injury or neurodegenerative disease. Total biomarker concentrations were determined from plasma samples using an ultra-sensitive detection method, Simoa™, and CRP was assayed by ELISA. Total tau and IL-6 concentrations were elevated in participants with moderate-severe OSA, with a mean apnea-hypopnea index (AHI) of 26.1/h, compared to those with mild OSA (mean AHI 8.6/h) and healthy controls (mean AHI 2.1/h). Tau concentrations were also significantly correlated with the AHI (r = 0.342, p = 0.004). Our findings show that tau is elevated in the blood of young patients with moderate-severe OSA, suggesting that this degree of sleep-disordered breathing is a contributing factor in the development of neurodegenerative disorders. The finding of increased IL-6 further suggests that inflammatory biomarkers are present early in the course of this chronic disease.

Periodontal disease, sleep duration, and white blood cell markers in the 2009 to 2014 National Health and Nutrition Examination Surveys

“…24 Previously conducted cross-sectional, casecontrol, prospective cohort studies as well as randomized controlled trials provided evidence for a positive association between sleep behaviors and inflammatory mediators such as CRP, IL-6, IL-8, TNF-, and von Willebrand factor antigen. 20,32,35,37,40,41,47 However, these studies were heterogeneous with respect to target population as well as definition of sleep behavior, with the majority focused on OSA. We found that hours of sleep were not related to WBC markers, after controlling for sociodemographics, lifestyle, and health characteristics, including periodontitis.…”

“…A priori confounders for the hypothesized relationships were identified based on the existing literature 16,20,25,26,28,29,[31][32][33][34][35][36][37][38][39][40][41] and classified as sociodemographic, lifestyle, and healthrelated characteristics. Sociodemographic characteristics included age (in years; 30 to 34, 35 to 39, 40 to 44, 45 to 49, 50 to 54, 55 to 59, 60 to 64, 65 to 96, and ≥70), race (Mexican American, other Hispanic, non-Hispanic white, non-Hispanic black, and other), education (<high school, 9th to 11th grade, high school graduate/GED or equivalent, some college or AA degree, college graduate or higher), marital status (married/living with partner, other) and poverty income ratio (<100%, 100% to <200%, and ≥200%).…”

Concurrent Mild Traumatic Brain Injury and Posttraumatic Stress Disorder Is Associated With Elevated Tau Concentrations in Peripheral Blood Plasma

“…Sleep disturbances have also been linked to increased symptom reporting and have been shown to hinder recovery following TBI (White et al., ). Finally, there is converging evidence that sleep affects protein concentrations in the central nervous system, including in terms of alterations in levels of both tau and Aβ (Ju et al., ; Motamedi et al., ). Sleep is the clearance mechanism for the glymphatic system, ridding the brain of excess proteins, including tau (Iliff et al., ; Louveau et al., ).…”

Biomarkers of dementia in obstructive sleep apnea

“…In young adults, whereas OSA was not associated with blood Aβ 42 and Aβ 40 levels, moderatesevere OSA was associated with increased blood total tau levels compared to both mild OSA and controls [70]. In another study, middle-aged OSA subjects had significantly higher blood Aβ 40 and Aβ 42 levels as well as phosphorylated tau levels compared to controls, although unchanged total tau levels were observed [71].…”