Monitoring neurodegeneration through brain-derived extracellular vesicles in biofluids

The identification of neurodegenerative disease (ND) biomarkers in easily accessible body fluids is crucial in the fight against this class of disorders. Brain-derived extracellular vesicles (BDEVs) have gained attention as nanoscale carriers of molecular information and bioactive molecules that reflect the status of their source cells. By crossing the blood-brain barrier (BBB), BDEVs can transfer these biomolecular signatures to peripheral biofluids, setting the scene for their use as ND biomarkers. In this review, we explore the role of BDEVs in liquid biopsy as a promising route for early ND diagnosis, as well as patient stratification and follow-up, with a particular focus on their ability to transport misfolded proteins and protein aggregates, major actors in neurodegeneration development. We also discuss the link between the physicochemical properties of BDEVs and the potential insights gained into NDs, highlighting both challenges and opportunities associated with the use of BDEVs for ND diagnostics.