Several differentially expressed proteins were diagnosis-confirming or reflecting the disease manifestation, for example, proteins associated with bleeding in the brain29 (CPVL, ISLR2, NXPH, FAM20, MASP1 and C1QTNF; Fig. 4b), predicted biomarkers of symptomatic CCM hemorrhage30 (for example, MMP2, CD14, PLXDC2, SPARC and IL6ST) or astroglial proteins (for example, S100B, GFAP, CD44, ALDOC and APOE) known for fast release into circulation after the BBB rupture1,15 detected exclusively enriched in CSF-CCM (Fig. 4c and Supplementary Table 4). This evidence concerns the gene ISLR2 and cerebral cavernous malformation.