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However, full methodological validation requires demonstration of L1CAM in individual NDEVs and lower levels or absence of L1CAM in individual EVs from other cells. Here, we used multiple single\u2010EV techniques to establish the neuronal origin and determine the abundance of L1CAM\u2010positive EVs in human blood. L1CAM epitopes of the ectodomain are shown to be co\u2010expressed on single\u2010EVs with the neuronal proteins \u03b2\u2010III\u2010tubulin, GAP43, and VAMP2, the levels of which increase in parallel with the enrichment of L1CAM\u2010positive EVs. Levels of L1CAM\u2010positive EVs carrying the neuronal proteins VAMP2 and \u03b2\u2010III\u2010tubulin range from 30% to 63%, in contrast to 0.8%\u20133.9% of L1CAM\u2010negative EVs. Plasma fluid\u2010phase L1CAM does not bind to single\u2010EVs. Our findings support the use of L1CAM as a target for isolating plasma NDEVs and leveraging their cargo to identify biomarkers reflecting neuronal function.<\/jats:p>","DOI":"10.1002\/jev2.12459","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T04:55:00Z","timestamp":1718254500000},"source":"Crossref","is-referenced-by-count":104,"title":["Single\u2010extracellular vesicle (EV) analyses validate the use of L1 Cell Adhesion Molecule (L1CAM) as a reliable biomarker of neuron\u2010derived EVs"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2503-965X","authenticated-orcid":false,"given":"Carlos J","family":"Nogueras\u2010Ortiz","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Investigation, Intramural Research Program National Institute on Aging, National Institutes of Health (NIA\/NIH)  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5190-9500","authenticated-orcid":false,"given":"Erden","family":"Eren","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation, Intramural Research Program National Institute on Aging, National Institutes of Health (NIA\/NIH)  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Yao","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation, Intramural Research Program National Institute on Aging, National Institutes of Health (NIA\/NIH)  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Calzada","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Investigation, Intramural Research Program National Institute on Aging, National Institutes of Health (NIA\/NIH)  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Dunn","sequence":"additional","affiliation":[{"name":"Flow Cytometry Unit, Intramural Research Program National Institute on Aging, National Institutes of Health (NIA\/NIH)  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1381-5543","authenticated-orcid":false,"given":"Olga","family":"Volpert","sequence":"additional","affiliation":[{"name":"NeuroDex Inc.  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