Serum Exosomal Proteins F9 and TSP-1 as Potential Diagnostic Biomarkers for Newly Diagnosed Epilepsy

Abstract

Epilepsy is one of the most common chronic neurological diseases in the world, with a high incidence, a high risk of sudden unexplained death, and diagnostic challenges. Exosomes are nanosized extracellular vesicles that are released into physical environments and carry a variety of biological information. Moreover, exosomes can also be synthesized and released from brain cells, passing through the blood-brain barrier, and can be detected in peripheral blood or cerebrospinal fluid. Our study using the tandem mass tag (TMT) approach showed that a total of 76 proteins were differentially expressed in serum exosomes between epilepsy patients and healthy controls, with 6 proteins increasing and 70 proteins decreasing. Analysis of large clinical samples and two mouse models of chronic epilepsy indicated that two significantly differentially expressed serum exosomal proteins, coagulation factor IX (F9) and thrombospondin-1 (TSP-1), represent promising biomarkers for the diagnosis of epilepsy, with area under the curve (AUC) values of up to 0.7776 (95% CI, 0.7306–0.8246) and 0.8534 (95% CI, 0.8152–0.8916), respectively. This is the first study of exosomal proteins in epilepsy, and it suggests that exosomes are promising new tools for the diagnosis of epilepsy.