Abstract
The blood-brain barrier (BBB) is hypothesized to play a role in the pathophysiology of psychosis. However, studying this structure in living humans is challenging due to limitations in current methods that fail to identify subtle changes or dysfunctions. Moreover, obtaining a biopsy is too invasive. To address these challenges, we aimed to isolate BBB-derived extracellular vesicles as potential biomarkers for neuropsychiatric conditions, providing a “liquid biopsy of the BBB”. Individuals with psychosis and healthy controls were recruited for this study. In the absence of single specific proteins for brain endothelial cells, we targeted three distinct proteins for immunolabelling. Proteomics and flow cytometry confirmed the presence of EV with the signature CD45-/CD31+/GLUT1+. Our efforts to generate adequate material for confirming proteomic analysis of EV with this signature were terminated due to excessive time and resource demands. This setback led us to recognize that our current approach was not feasible due to low abundance of EVs with the target signature. Moreover, the relative abundance of putative blood-derived EVs in comparison to putative brain endothelial cells (BEC)-derived EVs contradicted previously published data, raising concerns about the specificity of our approach.