Synaptic and complement markers in extracellular vesicles in multiple sclerosis.

Multiple Sclerosis : Clinical and Laboratory Research
Pavan BhargavaDimitrios Kapogiannis

Abstract

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. 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. 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. We found lower levels of NEV synaptopodin and synaptophysin in MS compared to controls (p < 0.0001 for both). In AEVs, we found higher levels of multiple complement cascade components in people with MS compared to controls; these differences were not noted in total EVs or neat plasma. Strikingly, there were strong inverse correlations between NEV synaptic proteins and multiple AEV complement components in MS, but ...Continue Reading

References

Dec 18, 2007·Cell·Beth StevensBen A Barres
Apr 28, 2010·Brain : a Journal of Neurology·Gillian IngramBryan Paul Morgan
Mar 30, 2011·Annals of Neurology·Ranjan DuttaBruce D Trapp
May 7, 2011·Molecular Immunology·Robert VeerhuisAndrea J Tenner
Feb 23, 2012·Multiple Sclerosis : Clinical and Laboratory Research·G IngramB P Morgan
Sep 7, 2013·Journal of Extracellular Vesicles·Kenneth W WitwerFred Hochberg
Oct 29, 2013·Seminars in Nephrology·Marina Noris, Giuseppe Remuzzi
Jun 3, 2014·Acta Neuropathologica Communications·Gillian IngramB Paul Morgan
Aug 19, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Massimo S FiandacaEdward J Goetzl
Oct 25, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Dimitrios KapogiannisEdward J Goetzl
Mar 3, 2015·Annals of Neurology·Iliana MichailidouValeria Ramaglia
Oct 28, 2015·Nature Neuroscience·Won-Suk ChungBeth Stevens
Nov 21, 2015·Nature Reviews. Neurology·Georgia MandolesiDiego Centonze
Dec 17, 2015·Brain : a Journal of Neurology·Tanja JürgensDoron Merkler
Jun 24, 2016·Journal of Neuroinflammation·Lewis M WatkinsOwain W Howell
Sep 8, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Edward J GoetzlBruce L Miller
Jan 19, 2017·Nature·Shane A LiddelowBen A Barres
Jun 8, 2017·Frontiers in Neuroscience·Maja MustapicDimitrios Kapogiannis
Dec 1, 2017·Journal of Extracellular Vesicles·Kenneth W WitwerClotilde Théry
Jan 11, 2018·The New England Journal of Medicine·Daniel S ReichPeter A Calabresi
Feb 7, 2018·Annals of Neurology·Edward J GoetzlDimitrios Kapogiannis
Jan 4, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Edward J GoetzlAurélie Ledreux
Jul 11, 2019·Brain : a Journal of Neurology·Kathryn C FitzgeraldPeter A Calabresi
Aug 20, 2019·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Longfei JiaJianping Jia

❮ Previous
Next ❯

Citations

Nov 27, 2020·Journal of Neuroinflammation·Nicole D Schartz, Andrea J Tenner
Dec 12, 2020·Frontiers in Cell and Developmental Biology·Kyoung Mi KimMyriam Gorospe
Mar 2, 2021·Annals of Clinical and Translational Neurology·Christian W KellerJan D Lünemann
Aug 8, 2021·International Journal of Molecular Sciences·Ainhoa AlberroDavid Otaegui
Aug 28, 2021·International Journal of Molecular Sciences·María Gutiérrez-FernándezLaura Otero-Ortega
Dec 15, 2020·Multiple Sclerosis : Clinical and Laboratory Research·Angeliki G FilippatouPavan Bhargava

❮ Previous
Next ❯

Methods Mentioned

BETA
blood draw
enzyme-linked immunosorbent assays
ELISA
ELISAs
blood collection

Software Mentioned

xPOTENT
GraphPad Prism
Stata

Related Concepts

Related Feeds

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.