Suchergebnisse

The article of record as published may be found at http://dx.doi.org/10.1016/j.sleep.2017.11.1121 ; 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 (Ab), is associated with neurodegenerative processes. We sought to determine if tau and other biomarkers of inflammation were related to OSA severity. Concentrations of tau, Ab40, Ab42, c-reactive protein (CRP), TNF-a, interleukin (IL)-6, and IL-10 were measured in blood and compared between participants with moderate-severe OSA (n 1⁄4 28), those with mild OSA (n 1⁄4 22), and healthy controls (n 1⁄4 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, SimoaTM, 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 1⁄4 0.342, p 1⁄4 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.

Symptoms of post-traumatic stress disorder (PTSD) are common in military populations, and frequently associated with a history of combat-related mild traumatic brain injury (mTBI). In this study, we examined relationships between severity of PTSD symptoms and levels of extracellular vesicle (EV) proteins and miRNAs measured in the peripheral blood in a cohort of military service members and Veterans (SMs/Vs) with chronic mTBI(s). Participants (n = 144) were divided into groups according to mTBI history and severity of PTSD symptoms on the PTSD Checklist for DSM-5 (PCL-5). We analyzed EV levels of 798 miRNAs (miRNAs) as well as EV and plasma levels of neurofilament light chain (NfL), Tau, Amyloid beta (Aβ) 42, Aβ40, interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNFα), and vascular endothelial growth factor (VEGF). We observed that EV levels of neurofilament light chain (NfL) were elevated in participants with more severe PTSD symptoms (PCL-5 ≥ 38) and positive mTBI history, when compared to TBI negative controls (p = 0.024) and mTBI participants with less severe PTSD symptoms (p = 0.006). Levels of EV NfL, plasma NfL, and hsa-miR-139–5p were linked to PCL-5 scores in regression models. Our results suggest that levels of NfL, a marker of axonal damage, are associated with PTSD symptom severity in participants with remote mTBI. Specific miRNAs previously linked to neurodegenerative and inflammatory processes, and glucocorticoid receptor signaling pathways, among others, were also associated with the severity of PTSD symptoms. Our findings provide insights into possible signaling pathways linked to the development of persistent PTSD symptoms after TBI and biological mechanisms underlying susceptibility to PTSD.

Traumatic brain injury (TBI) can be associated with long-term neurobehavioral symptoms. Here, we examined levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in extracellular vesicles isolated from blood, and their relationship with TBI severity and neurobehavioral symptom reporting. Participants were 218 service members and veterans who sustained uncomplicated mild TBIs (mTBI, n = 107); complicated mild, moderate, or severe TBIs (smcTBI, n = 66); or Injured controls (IC, orthopedic injury without TBI, n = 45). Within one year after injury, but not after, NfL was higher in the smcTBI group than mTBI (p = 0.001, d = 0.66) and IC (p = 0.001, d = 0.35) groups, which remained after controlling for demographics and injury characteristics. NfL also discriminated the smcTBI group from IC (AUC:77.5%, p < 0.001) and mTBI (AUC:76.1%, p < 0.001) groups. No other group differences were observed for NfL or GFAP at either timepoint. NfL correlated with post-concussion symptoms (r(s) = − 0.38, p = 0.04) in the mTBI group, and with PTSD symptoms in mTBI (r(s) = − 0.43, p = 0.021) and smcTBI groups (r(s) = − 0.40, p = 0.024) within one year after injury, which was not confirmed in regression models. Our results suggest the potential of NfL, a protein previously linked to axonal damage, as a diagnostic biomarker that distinguishes TBI severity within the first year after injury.