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Front Neurosci. 2017 May 22;11:278. doi: 10.3389/fnins.2017.00278. eCollection 2017.

Plasma Extracellular Vesicles Enriched for Neuronal Origin: A Potential Window into Brain Pathologic Processes.

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Intramural Research Program, Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health (NIA/NIH)Baltimore, MD, United States.
Department of Neurology, Johns Hopkins School of Medicine, Johns Hopkins UniversityBaltimore, MD, United States.
Department of Medicine, University of California, San FranciscoSan Francisco, CA, United States.
Jewish Home of San FranciscoSan Francisco, CA, United States.


Our team has been a pioneer in harvesting extracellular vesicles (EVs) enriched for neuronal origin from peripheral blood and using them as a biomarker discovery platform for neurological disorders. This methodology has demonstrated excellent diagnostic and predictive performance for Alzheimer's and other neurodegenerative diseases in multiple studies, providing a strong proof of concept for this approach. Here, we describe our methodology in detail and offer further evidence that isolated EVs are enriched for neuronal origin. In addition, we present evidence that EVs enriched for neuronal origin represent a more sensitive and accurate base for biomarkers than plasma, serum, or non-enriched total plasma EVs. Finally, we proceed to investigate the protein content of EVs enriched for neuronal origin and compare it with other relevant enriched and non-enriched populations of plasma EVs. Neuronal-origin enriched plasma EVs contain higher levels of signaling molecules of great interest for cellular metabolism, survival, and repair, which may be useful as biomarkers and to follow response to therapeutic interventions in a mechanism-specific manner.


Alzheimer's disease; biological markers; extracellular vesicles (EVs); liquid biopsy diagnostics; phosphorylated tau protein

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