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Peer-reviewedCC BYNature Neuroscience

Identification of candidate markers for the isolation of neuron-specific extracellular vesicles

5 more authors
14 affiliations
  1. 1Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA. [email protected]
  2. 2Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA
  3. 3Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
  4. 4Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
  5. 5Genentech, South San Francisco, CA, USA
  6. 6Broad Institute of MIT and Harvard, Cambridge, MA, USA
  7. 7Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected]
  8. 8Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. [email protected]
  9. 9Genentech, South San Francisco, CA, USA. [email protected]
  10. 10Harvard Medical School, Boston, MA, USA. [email protected]
  11. 11Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA. [email protected]
  12. 12Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. [email protected]
  13. 13Harvard Medical School, Boston, MA, USA. [email protected]
  14. 14Wyss Institute for Biologically Inspired Engineering, Boston, MA, USA. [email protected]

Abstract

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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BibTeX
@article{terovanesyan2026identification,
  title = {{Identification of candidate markers for the isolation of neuron-specific extracellular vesicles}},
  author = {Dmitry Ter‐Ovanesyan and Sara T. Whiteman and Tal Gilboa and Emma J. K. Kowal and Wendy Trieu and Siddharth Iyer and Bogdan Budnik and Clarissa May Babila and Chungmin Han and David Vance and Graham Heimberg and Michael William. Burgess and Hasmik Keshishian and Steven A. Carr and Aviv Regev and George McDonald Church and David R. Walt},
  journal = {Nature Neuroscience},
  year = {2026},
  month = oct,
  doi = {10.1038/s41593-026-02466-y},
  url = {https://doi.org/10.1038/s41593-026-02466-y},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Identification of candidate markers for the isolation of neuron-specific extracellular vesicles
AU  - Dmitry Ter‐Ovanesyan
AU  - Sara T. Whiteman
AU  - Tal Gilboa
AU  - Emma J. K. Kowal
AU  - Wendy Trieu
AU  - Siddharth Iyer
AU  - Bogdan Budnik
AU  - Clarissa May Babila
AU  - Chungmin Han
AU  - David Vance
AU  - Graham Heimberg
AU  - Michael William. Burgess
AU  - Hasmik Keshishian
AU  - Steven A. Carr
AU  - Aviv Regev
AU  - George McDonald Church
AU  - David R. Walt
PY  - 2026
DA  - 2026/10/23
JO  - Nature Neuroscience
DO  - 10.1038/s41593-026-02466-y
UR  - https://doi.org/10.1038/s41593-026-02466-y
AB  - 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.
SN  - 1097-6256
SN  - 1546-1726
ER  -