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Synaptic Protein Loss in Extracellular Vesicles Reflects Brain and Retinal Atrophy in People With Multiple Sclerosis
Dimitrios C Ladakis1, Michael Vreones1, Joseph Blommer1
1From the Department of Neurology (D.C.L., K.L.H., M.D.S., E.S.V., H.M., G.A., O.E., A.L.D., B.E.D., K.C.F., E.S.S., S.S., P.A.C., P.B.), Johns Hopkins University School of Medicine; Laboratory of Clinical Investigation (M.V., J.B., D.K.), National Institute on Aging; and Department of Electrical and Computer Engineering (J.L.P.), Johns Hopkins University, Baltimore, MD.
Changes in synaptic proteins from neuronally enriched extracellular vesicles (NEVs) correlate with brain and retinal atrophy in multiple sclerosis (MS) patients. These findings suggest NEV proteins may serve as biomarkers for MS neurodegeneration.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Multiple Sclerosis Research
Background:
- Multiple Sclerosis (MS) is a chronic neurological disease characterized by neurodegeneration.
- Current methods for monitoring MS progression often involve invasive imaging techniques.
- Identifying reliable circulating biomarkers for neurodegeneration in MS is crucial for effective disease management.
Purpose of the Study:
- To investigate the association between the rate of change in synaptic proteins within neuronally enriched extracellular vesicles (NEVs) and the progression of brain and retinal atrophy in individuals with MS.
- To explore the potential of NEV-derived synaptic proteins as indicators of neurodegenerative processes in MS.
Main Methods:
- Longitudinal study involving 50 individuals with MS, with serial blood draws, MRI, and optical coherence tomography (OCT) scans.
- Immunocapture of NEVs from plasma, followed by ELISA measurement of synaptopodin and synaptophysin.
- Correlation analysis between subject-specific rates of change in synaptic proteins and rates of brain and retinal atrophy.
Main Results:
- The rate of change in NEV synaptopodin was significantly associated with atrophy in the whole brain, cortical gray matter, and specific retinal layers (retinal nerve fiber layer, ganglion cell/inner plexiform layer).
- The rate of change in NEV synaptophysin also showed significant correlations with whole brain and cortical gray matter atrophy.
- These correlations suggest a link between synaptic protein dynamics in NEVs and neurodegenerative changes in MS.
Conclusions:
- NEV-derived synaptic proteins, including synaptopodin and synaptophysin, appear to reflect ongoing neurodegeneration in MS.
- These proteins hold promise as accessible, circulating biomarkers for monitoring disease progression and neurodegenerative changes in multiple sclerosis.
