Single-extracellular vesicle (EV) analyses validate the use of L1 Cell Adhesion Molecule (L1CAM) as a reliable biomarker of neuron-derived EVs.

Autor: Nogueras-Ortiz CJ; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Eren E; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Yao P; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Calzada E; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Dunn C; Flow Cytometry Unit, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Volpert O; NeuroDex Inc., Natick, Maryland, USA., Delgado-Peraza F; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Mustapic M; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Lyashkov A; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Rubio FJ; Neuronal Ensembles in Addiction Section, Behavioral Neuroscience Research Branch, Intramural Research Program/National Institute on Drug Abuse/National Institutes of Health, Baltimore, Maryland, USA., Vreones M; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA., Cheng L; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia., You Y; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.; Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA., Hill AF; La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia.; Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia., Ikezu T; Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.; Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA., Eitan E; NeuroDex Inc., Natick, Maryland, USA., Goetzl EJ; Department of Medicine, University of California, San Francisco, California, USA.; San Francisco Campus for Jewish Living, San Francisco, California, USA., Kapogiannis D; Laboratory of Clinical Investigation, Intramural Research Program, National Institute on Aging, National Institutes of Health (NIA/NIH), Baltimore, Maryland, USA.; Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: Journal of extracellular vesicles [J Extracell Vesicles] 2024 Jun; Vol. 13 (6), pp. e12459.
DOI: 10.1002/jev2.12459
Abstrakt: Isolation of neuron-derived extracellular vesicles (NDEVs) with L1 Cell Adhesion Molecule (L1CAM)-specific antibodies has been widely used to identify blood biomarkers of CNS disorders. 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-EV techniques to establish the neuronal origin and determine the abundance of L1CAM-positive EVs in human blood. L1CAM epitopes of the ectodomain are shown to be co-expressed on single-EVs with the neuronal proteins β-III-tubulin, GAP43, and VAMP2, the levels of which increase in parallel with the enrichment of L1CAM-positive EVs. Levels of L1CAM-positive EVs carrying the neuronal proteins VAMP2 and β-III-tubulin range from 30% to 63%, in contrast to 0.8%-3.9% of L1CAM-negative EVs. Plasma fluid-phase L1CAM does not bind to single-EVs. Our findings support the use of L1CAM as a target for isolating plasma NDEVs and leveraging their cargo to identify biomarkers reflecting neuronal function.
(© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)
Databáze: MEDLINE
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