Cell division cycle 42 binding protein beta as a plasma-based biomarker for cerebral cavernous malformations

OBJECTIVE: Cerebral cavernous malformations (CCMs) are groups of blood vessels that develop abnormally in both the brain and/or spinal cord. Currently, MRI and/or CT are the primary methods for assessing CCMs. Plasma-based biomarkers could serve as a complement to standard imaging techniques by providing a quantitative and molecular-based technique to detect disease at lower cost. Therefore, the authors evaluated cell division cycle 42 binding protein beta (CDC42BPB) as a potential novel plasma biomarker for CCMs. METHODS: Plasma samples were obtained from patients with pathological analysis-confirmed CCM (n = 10, age 1-16 years) and compared to controls (n = 24, age 1-19 years). The protein levels were measured using the Olink Proximity Extension Assay. Findings were confirmed with ELISA. CDC42BPB expression was further analyzed with Western blot and immunohistochemistry analysis in patient-derived primary cells and CCM tissues, respectively. RESULTS: CCM patients exhibited significantly higher CDC42BPB plasma levels compared to controls (approximately 6-fold greater expression, p = 0.004). Furthermore, the high CDC42BPB plasma expression was concordant with the protein levels in CCM tissues and patient-derived primary cells. CONCLUSIONS: The authors present data supporting the measurement of CDC42BPB plasma level as a putative biomarker for CCMs. These findings have implications relevant to improving diagnosis, follow-up, and molecular pathophysiological analysis.