Identification of candidate markers for the isolation of neuron-specific extracellular vesicles
Open accessAbstract
Extracellular vesicles (EVs) are present in biofluids and may be useful biomarkers to non-invasively monitor brain cells, but isolating cell type-specific EVs remains challenging. 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 + 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.
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Fiandaca, M. S., Kapogiannis, D., Mapstone, M., Boxer, A., Eitan, E., Schwartz, J. B., Abner, E. L., Petersen, R. C., Federoff, H. J., Miller, B. L., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.06.008 · Cited by 959 · see citing works
Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing
Treutlein, B., Gokce, O., Quake, S. R., & Südhof, T. C. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1403244111 · Cited by 348 · see citing works
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- Authors
- Ter-Ovanesyan, D., Whiteman, S., Gilboa, T., Kowal, E. J. K., Trieu, W., Iyer, S., Budnik, B., Babila, C. M., Han, C., Vance, D., Heimberg, G., Burgess, M. W., Keshishian, H., Carr, S. A., Regev, A., Church, G. M., & Walt, D. R.
- Affiliations
- Wyss Institute for Biologically Inspired Engineering (US)
- Genentech (US)
- Broad Institute (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Regev, Aviv
- Church, George M.
- Walt, David R.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2026-10-23
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W7223400515
- Cited by
- 0
- References
- 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Neuroscience (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Open Philanthropy Project
- Good Ventures Foundation
- National Institutes of Health
- Klarman Cell Observatory, Broad Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- extracellular vesicles, cell surface markers, NRXN3, cerebrospinal fluid, plasma, astrocytes, oligodendrocytes, microglia, EV proteome, transmembrane proteins
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