NO MUTATIONS IN CYSTATIN-C GENE IN CEREBRAL AMYLOID ANGIOPATHY WITH CYSTATIN-C DEPOSITION

To investigate the relationship between cerebral amyloid angiopathy (C AA) and cystatin C, we studied five CAA patients on whose cerebral blo od vessels colocalization of cystatin C and beta-protein was recognize d immunohistochemically. One patient was suspected as familial CAA and the other patients were sporadic cases. Two patients had low concentr ation of cystatin C in their cerebrospinal fluid (CSF) as we have prev iously reported in CAA patients. Enzyme-linked immunosorbent assay (EL ISA) revealed that cystatin C and beta-protein have been included at t he ratio of about 1:100 in the crude amyloid fibrils of one patient. U sing a monoclonal antibody (MAb) against cystatin C, we performed affi nity chromatography and immunoblotting on her amyloid fibril fraction. Eluate showed a band with a mol wt of 14,000 and the N-terminal 14 am ino acid residues of 14-kDa protein were identical with that of cystat in C. This molecular weight is not identical to that of the truncated form of cystatin C deposited in hereditary cerebral hemorrhage with am yloidosis in Iceland (HCKWA-I), but that of normal cystatin C. DNA seq uence analysis of five patients showed no point mutations in the cysta tin C gene. Cystatin C and beta-protein colocalization, which was reco gnized in amyloid lesions of CAA, suggests that cystatin C deposition may be related to beta-protein deposition. We hypothesize that cystati n C deposition in sporadic cerebral amyloid angiopathy with cystatin C deposition (SCCAA) involves a different mechanism from that in HCHWA- I, which may be related to low CSF concentration of cystatin C without amino acid substitutions.