Identifying central nervous system protein markers on extracellular vesicles to facilitate brain disease and injury diagnosis
Current diagnostic measurements for the central nervous system, such as imaging and biopsy, prove to be insufficient or impractical for early screening because they yield indeterminate information or rely on invasive procedures. A less invasive and more sensitive approach, through the use of biomarkers in the blood, would improve this process considerably. The blood contains extracellular vesicles (EVs) from every tissue in the body as well as circulating protein-complexed RNAs. If we could identify brain-enriched proteins on the surface of EVs, we could increase sensitivity for determining which EVs originate from the central nervous system. We could then use these proteins to enrich for cellular cargo, such as RNA and DNA, that comes directly from the brain. Currently, researchers use the protein L1CAM as an EV marker to probe for information from the brain. However, L1CAM is found in many other tissues of the body in addition to the brain and thus does not allow for definitive enrichment of brain-specific cargo. To identify better candidate proteins that would represent information from the brain more specifically, we mined data from the Human Protein Atlas. We then searched for the presence of two brain-specific EV membrane proteins (TAGLN3 and SEPT3) and the RNA protein complex of Ago2 in vesicles and vesicle-depleted plasma samples.