Detection of complement factor B in the cerebrospinal fluid of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy disease using two-dimensional gel electrophoresis and mass spectrometry

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leuk oencephalopathy (CADASIL) is a hereditary condition with onset in mid-adult hood and is associated with mutations in the Notch-3 gene. (Joutel, A., Cor epechot, C., Ducros, A., Vahedi, K., Chabriat, H., Mouton, P., Alamowitch, S., Domenda, V., Cecilion, M., Marechal, J., Vayssiere, C., Cruaud, C., Cab anis, E.A., Ruchoux, M.M., Weissenbach, J., Each, J.F., Bousser, M.G. and T ournier Lasserve, E., Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature, 383 (1996) 707-710). Ultras tructural examination of the pathology of the cerebral infarcts reveals dep osits in the vascular smooth muscle cells of the small arteries of the brai n, but there is no obvious indication how the Notch-3 mutations give rise t he observed pathology, nor is there any information on the exact nature of the deposits. We have investigated cerebrospinal fluid (CSF) from three CAD ASIL cases with known mutations in Notch-3 using two-dimensional gel electr ophoresis. CSF from these patients was compared to that of six controls. We detected a single spot in the protein maps of patients which was absent fr om all the controls. In-gel tryptic digestion of this protein followed by m ass spectrometric analysis of the tryptic fragments and a database search i dentified the spot as human complement factor B. These preliminary findings suggest that the alternative complement pathway may play a role in the pat hogenesis of CADASIL. (C) 2000 Published by Elsevier Science Ireland Ltd. A ll rights reserved.