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Here we introduce an approach to immuno-isolate EVs from neurons and glia based on protein surface markers. We first selected transmembrane proteins suitable as cell type-specific EV markers based on gene expression and EV proteomic data. We developed a high-purity EV isolation method and cataloged the proteins present on EVs in human cerebrospinal fluid and plasma. We then computationally identified cell type-specific candidate markers for isolating EVs from neurons, astrocytes, oligodendrocytes and microglia. Using ultrasensitive immunoassays against several predicted neuron-specific proteins, we confirmed one marker, NRXN3, as present on EVs in cerebrospinal fluid and plasma. Finally, we developed efficient EV immuno-isolation methods and applied them to isolate NRXN3\n                    <jats:sup>+<\/jats:sup>\n                    EVs. Our work provides a general methodology for the isolation of cell type-specific EVs, advancing the goal of using EVs to study brain diseases.\n                  <\/jats:p>","DOI":"10.1038\/s41593-026-02466-y","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T09:01:38Z","timestamp":1792746098000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of candidate markers for the isolation of neuron-specific extracellular vesicles"],"prefix":"10.1038","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1134-0073","authenticated-orcid":false,"given":"Dmitry","family":"Ter-Ovanesyan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Whiteman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tal","family":"Gilboa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma J. 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A.R. is a founder and equity holder of Celsius Therapeutics, is an equity holder in Immunitas Therapeutics and, until 31 August 2020, was an SAB member of Syros Pharmaceuticals, Neogene Therapeutics, Asimov and Thermo Fisher Scientific. Since 1 August 2020, A.R. has been an employee of Genentech. D.R.W. has a financial interest in Quanterix Corporation. He is an inventor of the Simoa technology, a founder of the company and a member of its Board of Directors. D.R.W.\u2019s interests were reviewed and are managed by Mass General Brigham and Harvard University in accordance with their conflict of interest policies. The authors have filed IP on methods for EV isolation and analysis.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}