Synaptic and complement markers in extracellular vesicles in multiple sclerosis

Background: Synaptic loss is a feature of multiple sclerosis pathology that can be seen even in normal-appearing gray matter. Opsonization of synapses with complement components may underlie pathologic synapse loss. Objective: We sought to determine whether circulating neuronal-enriched and astrocyt...

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Bibliographic Details
Published in:Multiple sclerosis 2021-04, Vol.27 (4), p.509-518
Main Authors: Bhargava, Pavan, Nogueras-Ortiz, Carlos, Kim, Sol, Delgado-Peraza, Francheska, Calabresi, Peter A, Kapogiannis, Dimitrios
Format: Article
Language:English
Subjects:
Complement component C1q
Complement component C3
Complement component C3b
Complement component C4
Complement component C5a
Complement factor H
Complement system
Extracellular vesicles
Multiple sclerosis
Opsonization
Substantia grisea
Synapses
Synaptophysin
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Summary:Background: Synaptic loss is a feature of multiple sclerosis pathology that can be seen even in normal-appearing gray matter. Opsonization of synapses with complement components may underlie pathologic synapse loss. Objective: We sought to determine whether circulating neuronal-enriched and astrocytic-enriched extracellular vesicles (NEVs and AEVs) provide biomarkers reflecting complement-mediated synaptic loss in multiple sclerosis. Methods: From plasma of 61 people with multiple sclerosis (46 relapsing–remitting multiple sclerosis (RRMS) and 15 progressive MS) and 31 healthy controls, we immunocaptured L1CAM + NEVs and GLAST + AEVs. We measured pre- and post-synaptic proteins synaptopodin and synaptophysin in NEVs and complement components (C1q, C3, C3b/iC3b, C4, C5, C5a, C9, Factor B, and Factor H) in AEVs, total circulating EVs, and neat plasma. Results: We found lower levels of NEV synaptopodin and synaptophysin in MS compared to controls (p 
ISSN:1352-4585
1477-0970
DOI:10.1177/1352458520924590