Roughly 15% of individuals with multiple sclerosis (MS) present with a progressive course from the very beginning; this subtype, primary progressive (PP) MS, remains challenging regarding both diagnosis and management and is linked to unfavorable outcomes. Brain-derived extracellular vesicles (EVs) detectable in circulation, together with their internal proteins, may serve as indicators of disease processes. We examined whether the levels of MBP and MOG within oligodendrocyte-derived EVs (ODEVs) might operate as biomarkers for MS and assist in distinguishing clinical forms of the illness. In total, 136 participants were studied (7 CIS, 18 PPMS, 49 RRMS) along with 70 matched healthy controls (HC). ODEVs were isolated from serum through immuno-capture using an anti-MOG antibody, and MBP/MOG cargoes were quantified by ELISA. MBP concentrations in ODEVs were markedly higher in CIS (p < 0.001), RRMS (p < 0.001) and PPMS (p < 0.001) when compared with HC and showed associations with EDSS and MSSS scores. Importantly, MBP content in PPMS was also significantly elevated relative to RRMS (p = 0.004) and CIS (p = 0.03). Logistic regression and ROC analyses supported these findings. A low-burden blood assay assessing MBP within ODEVs may represent a valuable adjunct for MS diagnostics.
