Plasma extracellular vesicles – a biomarker discovery platform for neurological disorders

A research team at the National Institute on Aging 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, the researchers describe their methodology in detail and offer further evidence that isolated EVs are enriched for neuronal origin. In addition, they 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, they 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.

Graphical workflow of the neuronal enrichment protocol


Created with GIMP

W/i signifies the addition of protease and phosphatase inhibitors containing 2–3x the concentration recommended by the manufacturer.

Mustapic M, Eitan E, Werner JK Jr, Berkowitz ST, Lazaropoulos MP, Tran J, Goetzl EJ, Kapogiannis D. (2017) Plasma Extracellular Vesicles Enriched for Neuronal Origin: A Potential Window into Brain Pathologic Processes. Front Neurosci 11:278. [article]

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