Background: Cellular prion protein (PrPC) is a lipid raft protein locallizing within CNS tissue. It is reguated by a disiintegrin and metaloproteinase domain containing protein 10 (ADAM10), which induces ectodomain shedding. PrPC has been previousy implicated as a ptentia lbiomarker for TBI, but no prior studies have examined the potential of ADAM10 as a biomarker. Methods: Serum samples from patients admitted for TBI were collected and patient data was recorded. Control serum was acquired from a commercial tissue bank. Patient GCS was recorded during admission. Serum was used for ELISA to assess PrPC and ADAM10 expression. GraphPad was used to conduct ANOVA and regressional analysis. Results: 37 control and 20 TBI samples were collected. Of the TBI patiients, 8 were mild, 3 were moderate, and 9 were severe cilnical grade. Both PrPC and ADAM10 were elevated in TBI patients compared with control (p<0.001). ADAM10 exhibited a dose response, with greter expression in patients with higher clinical grade. There was no significant association of either PrPC or ADAM10 with time after injury. Conclusions: Our results indicate that PrPC and ADAM10 may be useful tools for screening of TBI. ADAM10 is associated closely with clinlcal grade, and may in the future represent a promising prognostic tool.