Plasma Proteomic Biomarkers of Degenerative Cervical Myelopathy in the UK Biobank

BACKGROUND AND OBJECTIVES: The diagnosis of spinal cord dysfunction in degenerative cervical myelopathy (DCM) is currently based on correlating clinical signs and symptoms with neuroimaging findings. Plasma proteomics represents an opportunity to establish objective, blood-based biomarkers, which predict DCM severity or response to surgical intervention. These methods may also support novel insights into its pathophysiological relationship with other neurological diseases, such as multiple sclerosis (MS), which also can present with myelopathy, or peripheral neuropathy (PN), which has overlapping symptoms with DCM. In this study, we examined the relationships between circulating blood protein levels with DCM, MS, and PN using data from the UK Biobank Pharma Proteomics Project. METHODS: The plasma proteomic profiles of participants with a diagnosis of DCM within 5 years of blood draw, who had not undergone surgical intervention (n = 42) were compared with those without known neural injury or neurodegenerative disease (n = 39 519) using case-control matching. To further characterize the difference between central and peripheral nerve injury, case-control analyses were also performed using participants with a diagnosis of MS (n = 125) and PN (n = 101) within 5 years of blood draw. RESULTS: The top proteins significantly associated with DCM included neuron markers RNA-binding Fox-1 homolog 3 and neurofilament light chain. These proteins were also significantly elevated in the PN group relative to controls, and neurofilament light was elevated in MS. CONCLUSION: These findings suggest that neural injury in DCM can be detected using blood protein levels and may hold value in diagnostic, monitoring, and potentially prognostic applications.