Extracellular Vesicles Reveal Abnormalities In Neuronal Iron Metabolism In Restless Legs Syndrome.

Study ObjectivesDetermine abnormalities in levels of iron-management proteins in neuronal origin-enriched extracellular vesicles (nEVs) in Restless Legs Syndrome (RLS).

METHODS: We used immunoprecipitation for neuronal marker L1CAM to isolate nEVs from the serum of 20 RLS subjects from a study including MRI determinations of iron deposition in the substantia nigra and hematologic parameters and 28 age- and sex-matched Controls.

RESULTS: RLS compared to Control subjects showed higher levels of nEV total ferritin but similar levels of transferrin receptor and ferroportin. Western blot analysis showed that heavy- but not light-chain ferritin was increased in nEVs of RLS compared to Control subjects. In RLS but not Control subjects, nEV total ferritin was positively correlated with systemic iron parameters; the two groups also differed in the relation of nEV total ferritin to MRI-measures of iron deposition in substantia nigra.

CONCLUSIONS: Given the neuronal origin and diversity of EV cargo, nEVs provide an important platform for exploring the underlying pathophysiology and possible biomarkers of RLS.