Establishment of Neurofilament Light Chain in Plasma-Derived Neuronal Extracellular Vesicles as a Biomarker for Disease Progression in Multiple Sclerosis Patients

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Multiple sclerosis (MS) is a complex neurological disorder. Neurofilament light chain (NfL) is a marker of axonal injury. It is potentially a significant biomarker in MS. Its detection from neuron-derived extracellular vesicles (NDEVs) using enzyme-linked immunosorbent assay (ELISA) warrants further exploration. NDEVs displayed typical extracellular vesicle traits and neuronal markers. NfL levels rose significantly in SPMS/PPMS patients (3.41 ± 0.979 pg/mL, p < 0.001) compared to RRMS patients (1.16 ± 0.549 pg/mL). NfL’s potential to distinguish MS patients from controls and among disease types was confirmed (AUC = 0.6531 and 0.9938, respectively). Additionally, our study revealed that Disease-Modifying Therapies (DMTs) treatment correlates with reduced NfL levels (mean: 1.302 pg/mL) compared to untreated MS patients (mean: 2.446 pg/mL), as shown by an unpaired t-test (p = 0.0095). NfL levels were significantly associated with MS progression and EDSS deterioration, explaining 68.7 and 37.5% of the variance, respectively. MS disease type was a significant predictor of NfL variation in multivariate analysis. Age, gender, disease type, EDSS score and disease duration were included in the regression models. A strong correlation was found between NDEV NfL levels, EDSS scores, and MS disease progression, suggesting the potential of ELISA-based NfL quantification in NDEVs for MS diagnosis and monitoring.