Scientists described a tetraspanin-based immunocapture method that substantially increases proteomic depth for extracellular vesicles (EVs) isolated from cerebrospinal fluid (CSF). The technique enriches EV subpopulations via tetraspanin markers, enabling more comprehensive protein profiling from limited CSF volumes and improving biomarker discovery potential for neurological diseases. By combining targeted capture with high-sensitivity mass spectrometry, the workflow uncovers low-abundance EV proteins relevant to neurodegeneration and CNS oncology, offering a reproducible path for translational biomarker studies where sample availability is constrained.