Hypothesis
Extracellular vesicles shed by brain endothelial cells could be isolated from peripheral blood as a 'liquid biopsy' of the blood-brain barrier, giving a biomarker for psychosis.
What failed
Lacking a single specific brain-endothelial protein, the team immunolabelled three proteins and confirmed by proteomics and flow cytometry that vesicles with a CD45−/CD31+/GLUT1+ signature exist — but generating enough material to confirm the proteomic analysis demanded too much time and resource, and the work was stopped.
Broken assumption
Brain-endothelial extracellular vesicles are abundant and specifically identifiable enough in blood to serve as a blood-brain-barrier biopsy.
Why
The authors conclude the approach was not feasible because vesicles with the target signature are too scarce, and because the relative abundance of putative blood-derived versus brain-endothelial vesicles contradicted published data, raising doubts about the markers' specificity.
From the published paper: Tunset et al. Journal of Trial and Error, 2025. ↗CC BY