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Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
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Synaptic and complement markers in extracellular vesicles in multiple sclerosis.

Pavan Bhargava1, Carlos Nogueras-Ortiz2, Sol Kim1

  • 1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Multiple Sclerosis (Houndmills, Basingstoke, England)
|July 17, 2020
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Summary
This summary is machine-generated.

In multiple sclerosis (MS), lower synaptic proteins in neuronal extracellular vesicles (NEVs) and higher complement proteins in astrocytic extracellular vesicles (AEVs) suggest a link to synaptic loss.

Keywords:
Extracellular vesiclesastrocytesbiomarkerscomplementmultiple sclerosissynaptic dysfunction

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Area of Science:

  • Neuroscience
  • Immunology
  • Biomarker Discovery

Background:

  • Synaptic loss is a key feature of multiple sclerosis (MS) pathology, affecting even normal-appearing gray matter.
  • Complement-mediated opsonization of synapses is a potential mechanism driving this pathological synapse loss.

Purpose of the Study:

  • To investigate if circulating neuronal-enriched and astrocytic-enriched extracellular vesicles (NEVs and AEVs) can serve as biomarkers for complement-mediated synaptic loss in MS.
  • To explore the relationship between synaptic proteins and complement components in these extracellular vesicles.

Main Methods:

  • Immunocaptured NEVs and AEVs from plasma of 61 MS patients and 31 healthy controls.
  • Measured pre- and post-synaptic proteins (synaptopodin, synaptophysin) in NEVs.
  • Quantified complement components in AEVs, total EVs, and plasma.

Main Results:

  • Significantly lower levels of NEV synaptopodin and synaptophysin in MS patients compared to controls.
  • Elevated levels of multiple complement cascade components in AEVs of MS patients, not observed in total EVs or plasma.
  • Strong inverse correlations between NEV synaptic proteins and AEV complement components in MS, but not in controls.

Conclusions:

  • Circulating extracellular vesicles can identify synaptic loss in MS.
  • Findings suggest a potential link between astrocytic complement production and synaptic loss in multiple sclerosis.