CSF Proteins Associated With Neuroaxonal Damage in Early Active Multiple Sclerosis.

Area of Science:

• Neuroscience
• Immunology
• Biochemistry

Background:

• Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
• Neuroaxonal degeneration is a key pathological process in MS, contributing to irreversible disability.
• Neurofilament light (NfL) protein is a sensitive biomarker of neuroaxonal damage.

Purpose of the Study:

• To identify biological processes and protein patterns associated with neuroaxonal degeneration in MS.
• To analyze protein profiles in cerebrospinal fluid (CSF) and serum linked to neurofilament light (NfL) levels.

Main Methods:

• Used highly sensitive proximity extension assay technology to quantify protein levels in paired CSF and serum samples from early-stage MS patients.
• Stratified patients based on CSF-NfL levels and employed discovery and validation cohorts.
• Analyzed protein associations with CSF-NfL and serum NfL levels.

Main Results:

• Identified 13 proteins upregulated in CSF, with 6 (CCL19, CXCL11, MSR1, CXCL10, TNFRSF12A, CCL23) replicated in a validation cohort.
• Found 75 CSF proteins significantly associated with CSF-NfL levels.
• No consistent serum protein profiles associated with serum NfL levels were identified.

Conclusions:

• The identified CSF protein profile reveals distinct inflammatory processes linked to ongoing neuroaxonal degeneration in MS.
• The 6 replicated proinflammatory markers are independently relevant to MS pathogenesis.
• Findings may elucidate immunologic pathways underlying MS-related neuroaxonal damage.