Evidence map›Paper›PMID 41216884›Full record

ArticleJournal of extracellular vesicles2025

Extracellular Vesicles From Multiple Sclerosis White Matter Exhibit Synaptic, Mitochondrial, Complement and Ageing-Related Pathway Dysregulation.

Larissa Jank, Madathiparambil Kumaran Satheesh Kumar, Taekyung Ryu, Rohit Thapa, Olesia Gololobova, Timothy D Niepokny, Peter A Calabresi, Kenneth Witwer, Ranjan Dutta, Chan Hyun Na and 1 more

Abstract read
In one paragraph

Article in Journal of extracellular vesicles, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Larissa JankDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA.ORCID https://orcid.org/0009-0008-7316-8054
Madathiparambil Kumaran Satheesh KumarDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA.
Taekyung RyuInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, USA.
Rohit ThapaDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA.
Olesia GololobovaDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, USA.ORCID https://orcid.org/0000-0002-0392-268X
Timothy D NiepoknyDepartment of Neuroscience, Cleveland Clinic, Cleveland, USA.
Peter A CalabresiDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA.
Kenneth WitwerDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, USA.
Ranjan DuttaDepartment of Neuroscience, Cleveland Clinic, Cleveland, USA.
Chan Hyun NaInstitute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, USA.
Pavan BhargavaDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, USA.

Funding

Genentech Next-generation biomarkers grantMyelin Repair FoundationNational Multiple Sclerosis Society FG-2207-40205National Multiple Sclerosis Society JF-2007-36755
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are increasingly recognized as mediators of central nervous system (CNS) function and pathologies, including multiple sclerosis (MS). While plasma-derived EVs have been explored as biomarkers in MS, little is known about EVs in CNS tissue. Here, we characterize EVs from postmortem normal-appearing white matter (NAWM) of MS and control brains. EVs were separated by differential centrifugation followed by size exclusion chromatography and characterized using nanoflow cytometry, single-particle reflectance imaging sensing (SP-IRIS) and transmission electron microscopy. EV size, yield and morphology did not differ significantly between MS and control samples. Despite the small sample size (n = 4 per group), proteomic analyses revealed downregulation of synaptic and mitochondrial proteins and upregulation of complement and inflammatory proteins and pathways in MS NAWM EVs. This suggests that EVs reflect ongoing synaptic pathology, metabolic dysfunction and CNS-compartmentalized inflammation and that they may actively contribute to these pathological processes. Deconvolution analyses suggest a shift in EV cellular origin, with an increased astrocytic and decreased neuronal EV contribution in MS. Several proteomic changes we observed in CNS-derived EVs have also been reported in circulating EVs of people with MS, establishing this CNS tissue EV study as a valuable resource for identifying biomarker candidates for brain-derived plasma EV studies.

Indexed as

AgingComplement System ProteinsExtracellular VesiclesMitochondriaMultiple SclerosisSynapsesWhite MatterAdultAgedBiomarkersFemaleHumansMaleMiddle AgedProteomicsBiomarkersComplement System Proteinsbrain‐derived extracellular vesiclescomplement activationmitochondrial dysfunctionmultiple sclerosisnormal appearing white mattersynaptic pathologytissue‐derived extracellular vesicles

Identifiers

PMID41216884
PMCPMC12603783

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.