{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:28:31Z","timestamp":1791941311845,"version":"4.3.4"},"reference-count":77,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012159","name":"Myelin Repair Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012159","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["FG\u20102207\u201040205"],"award-info":[{"award-number":["FG\u20102207\u201040205"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["JF\u20102007\u201036755"],"award-info":[{"award-number":["JF\u20102007\u201036755"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","award":["Next\u2010generation biomarkers grant"],"award-info":[{"award-number":["Next\u2010generation biomarkers grant"]}],"id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Extracellular vesicles (EVs) are increasingly recognized as mediators of central nervous system (CNS) function and pathologies, including multiple sclerosis (MS). While plasma\u2010derived EVs have been explored as biomarkers in MS, little is known about EVs in CNS tissue. Here, we characterize EVs from postmortem normal\u2010appearing 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\u2010particle reflectance imaging sensing (SP\u2010IRIS) and transmission electron microscopy. EV size, yield and morphology did not differ significantly between MS and control samples. Despite the small sample size (\n                    <jats:italic>n<\/jats:italic>\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\u2010compartmentalized 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\u2010derived 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\u2010derived plasma EV studies.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70197","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:16:22Z","timestamp":1762859782000},"source":"Crossref","is-referenced-by-count":7,"title":["Extracellular Vesicles From Multiple Sclerosis White Matter Exhibit Synaptic, Mitochondrial, Complement and Ageing\u2010Related Pathway Dysregulation"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7316-8054","authenticated-orcid":false,"given":"Larissa","family":"Jank","sequence":"first","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madathiparambil Kumaran Satheesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taekyung","family":"Ryu","sequence":"additional","affiliation":[{"name":"Institute for Cell Engineering Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohit","family":"Thapa","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0392-268X","authenticated-orcid":false,"given":"Olesia","family":"Gololobova","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Niepokny","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Cleveland Clinic  Cleveland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Calabresi","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore USA"},{"name":"Solomon H. Snyder Department of Neuroscience Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Witwer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjan","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Cleveland Clinic  Cleveland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan Hyun","family":"Na","sequence":"additional","affiliation":[{"name":"Institute for Cell Engineering Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavan","family":"Bhargava","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine  Baltimore USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011625"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26157213"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12079"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35012083"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8091058"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520924590"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.05.095"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031365"},{"key":"e_1_2_13_10_1","unstructured":"Carlson M.2023. \u201cGO.db: A set of annotation maps describing the entire Gene Ontology.\u201d R package version 3.17.0.http:\/\/bioconductor.org\/packages\/GO.db."},{"key":"e_1_2_13_11_1","unstructured":"Carlson M.2023. \u201corg.Hs.eg.db: Genome wide annotation for Human.\u201d R package version 3.17.0.http:\/\/bioconductor.org\/packages\/org.Hs.eg.db."},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1007"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe5085"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03148-x"},{"key":"e_1_2_13_15_1","doi-asserted-by":"crossref","unstructured":"D'Arrigo G. G.Cutugno M. T.Golia et al.2025. \u201cMicroglial extracellular vesicles mediate C1q deposition at the pre\u2010synapse and promote synaptic pruning.\u201d bioRxiv [Preprint].","DOI":"10.1101\/2025.02.28.640756"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23708"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03243-z"},{"key":"e_1_2_13_18_1","article-title":"Comprehensive autopsy program for individuals with multiple sclerosis","volume":"149","author":"Dutta R.","year":"2019","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20736"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0479-z"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.626043"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-021-00730-1"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2024.112365"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18928"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad332"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2020.1785746"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/13524585221125381"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03147-y"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv353"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.27"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2015.09.019"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4256"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.05.002"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2018.1560808"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1850"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.148382"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200257"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.018"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2024.11.016"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.623039"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.05.011"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27293-5"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14230"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2219801120"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad1025"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-025-02923-1"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0114-2"},{"key":"e_1_2_13_48_1","unstructured":"Pag\u00e8s H. M.Carlson S.Falcon andN.Li.2023. \u201cAnnotation Dbi: Manipulation of SQLite\u2010based annotations in Bioconductor.\u201d R package version 1.62.2.http:\/\/bioconductor.org\/packages\/AnnotationDbi."},{"key":"e_1_2_13_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2023.578064"},{"key":"e_1_2_13_50_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001166"},{"key":"e_1_2_13_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07167-9"},{"key":"e_1_2_13_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9472"},{"key":"e_1_2_13_53_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1401483"},{"key":"e_1_2_13_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv007"},{"key":"e_1_2_13_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.970486"},{"key":"e_1_2_13_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32552-1"},{"key":"e_1_2_13_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12355"},{"key":"e_1_2_13_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28655-4"},{"key":"e_1_2_13_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2"},{"key":"e_1_2_13_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.7b07782"},{"key":"e_1_2_13_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2023.06.025"},{"key":"e_1_2_13_62_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200420"},{"key":"e_1_2_13_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12041"},{"key":"e_1_2_13_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"e_1_2_13_65_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2017.1369805"},{"key":"e_1_2_13_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.12.004"},{"key":"e_1_2_13_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00704-1"},{"key":"e_1_2_13_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"},{"key":"e_1_2_13_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2582"},{"key":"e_1_2_13_70_1","article-title":"clusterProfiler 4.0: A Universal Enrichment Tool for Interpreting Omics Data","volume":"2","author":"Wu T.","year":"2021","journal-title":"Innovation"},{"key":"e_1_2_13_71_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1204-7"},{"key":"e_1_2_13_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202301706"},{"key":"e_1_2_13_73_1","doi-asserted-by":"publisher","DOI":"10.1080\/20013078.2019.1706801"},{"key":"e_1_2_13_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.104554"},{"key":"e_1_2_13_75_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr110"},{"key":"e_1_2_13_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.11.013"},{"key":"e_1_2_13_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1854"},{"key":"e_1_2_13_78_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02258-z"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.70197","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:43:07Z","timestamp":1765186987000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jev2.70197"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":77,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/jev2.70197"],"URL":"https:\/\/doi.org\/10.1002\/jev2.70197","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"article-number":"e70197"}}