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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
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Extracellular Vesicles From Multiple Sclerosis White Matter Exhibit Synaptic, Mitochondrial, Complement and
Larissa Jank1, Madathiparambil Kumaran Satheesh Kumar1, Taekyung Ryu2
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA.
Journal of Extracellular Vesicles
|November 11, 2025
Summary
Extracellular vesicles (EVs) in multiple sclerosis (MS) brain tissue reveal synaptic and mitochondrial protein changes. These EVs may contribute to MS pathology and offer insights into brain-derived biomarkers.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Extracellular vesicles (EVs) are crucial in central nervous system (CNS) function and disease, including multiple sclerosis (MS).
- While plasma EVs are studied in MS, CNS tissue EVs remain undercharacterized.
- Normal-appearing white matter (NAWM) in MS brains offers a unique source for EV investigation.
Purpose of the Study:
- To characterize EVs from postmortem MS and control brain NAWM.
- To investigate proteomic differences in EVs between MS and control groups.
- To explore the potential role of CNS EVs in MS pathology and as biomarker sources.
Main Methods:
- EV isolation via differential centrifugation and size exclusion chromatography.
- EV characterization using nanoflow cytometry, SP-IRIS, and transmission electron microscopy.
- Proteomic analysis of isolated EVs from MS and control NAWM.
Main Results:
- No significant differences in EV size, yield, or morphology between MS and control groups.
- Proteomics revealed downregulated synaptic and mitochondrial proteins in MS NAWM EVs.
- Upregulated complement and inflammatory proteins/pathways were observed in MS NAWM EVs, suggesting CNS inflammation.
Conclusions:
- MS NAWM EVs reflect synaptic pathology, metabolic dysfunction, and CNS inflammation.
- EVs may actively contribute to MS pathological processes.
- Shifts in EV origin (increased astrocyte, decreased neuron) and proteomic changes in CNS EVs correlate with circulating MS EV findings, aiding biomarker discovery.
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