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Fatigue and daytime sleepiness are two of the most common chronic symptoms reported after traumatic brain injury (TBI). However, there is limited understanding of the pathophysiological mechanisms following TBI that result in these symptoms. Previous research has observed elevations in peripheral blood levels of proteins in TBI patients versus controls, including neurofilament light chain (NFL)—predominantly expressed in long myelinated subcortical axons—and glial fibrillary acidic protein (GFAP)—predominantly expressed in reactive astrocytes responding to central nervous system injuries. This study examines the relationship between serum and exosomal NFL and GFAP, and symptoms of fatigue and daytime sleepiness in TBI patients 1-year after injury. Methods Sixty-seven patients with TBIs ranging from mild to severe were included in this study. Blood samples were collected from all participants 1-year post TBI, with concentrations of GFAP and NFL measured in serum and exosomes using Single Molecule Array technology (Simoa), an ultrasensitive assay. Participants reported fatigue using the Fatigue Severity Scale (FSS), and daytime sleepiness using the Epworth Sleepiness Scale (ESS). Results A linear regression model of fatigue symptoms and exosomal NFL controlling for age revealed that fatigue was negatively associated with exosomal NFL concentrations (β = -.317, p = .041, ηp2 = -.343) and accounted for 20.2% of the change in NFL. Serum NFL concentrations were not associated with fatigue, nor were GFAP serum or exosomes. No significant associations were found between NFL, GFAP, and daytime sleepiness. Conclusion Our findings suggest that exosomal NFL may be related to mechanisms underlying TBI-related fatigue and the potential of NFL as a biomarker of fatigue. To our knowledge, this study is the first to examine the relationship between post-TBI NFL levels and fatigue symptoms. Further investigation into serum and exosome biomarkers of TBI-related fatigue and daytime sleepiness is warranted. Support National Institutes of Health and Center for Neuroscience and Regenerative Medicine

1118 Examining the Role of Serum and Exosomal Biomarkers in Symptoms of Fatigue and Daytime Sleepiness Following Traumatic Brain Injury