OBJECTIVES: alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) peptide, a product of the proteolytic degradation of AMPA receptors in healthy nonathletes and athletes with concussions, is assessed. The detection of AMPAR peptide in conjunction with neuropsychological testing and neuroimaging is undertaken. SUBJECTS: Persons (n = 124, 19-23 years) are enrolled in the pilot-blinded study according to approved Institutional Review Board protocols at Kennesaw State University and DeKalb Medical. METHODS: AMPAR peptide plasma assay was performed using magnetic particles-enzyme-linked immunosorbent assay. All participants had neurocognitive tests (ImPACT); selected subjects with concussions were followed-up with magnetic resonance imaging and neurologic consultations. RESULTS: Athletes (n = 33) with clinically defined single or multiple concussions were compared to 91 age and gender matched controls without a history of concussion. AMPAR peptide values of 0.05-0.40 ng/mL for controls and 1.0-8.5 ng/mL for concussions are found. The biomarker sensitivity of 91% and a specificity of 92% (0.4 ng/mL cut off) to assess concussions are calculated. Poorer ImPACT scores correlated with abnormal levels of the biomarker. In athletes with multiple concussions, increased AMPAR peptide values (2.0-12.0 ng/mL) were associated with minor findings on magnetic resonance imaging. CONCLUSION: AMPAR peptide assay combined with ImPACT and neuroimaging is a promising tool for assessment of concussions. Additional clinical validation studies are required.