No mutations in cystatin C gene in cerebral amyloid angiopathy with cystatin C deposition.
To investigate the relationship between cerebral amyloid angiopathy (CAA) and cystatin C, we studied five CAA patients on whose cerebral blood vessels colocalization of cystatin C and beta-protein was recognized immunohistochemically. One patient was suspected as familial CAA and the other patients were sporadic cases. Two patients had low concentration of cystatin C in their cerebrospinal fluid (CSF) as we have previously reported in CAA patients. Enzyme-linked immunosorbent assay (ELISA) revealed that cystatin C and beta-protein have been included at the ratio of about 1:100 in the crude amyloid fibrils of one patient. Using a monoclonal antibody (MAb) against cystatin C, we performed affinity chromatography and immunoblotting on her amyloid fibril fraction. Eluate showed a band with a mol wt of 14,000 and the N-terminal 14 amino acid residues of 14-kDa protein were identical with that of cystatin C. This molecular weight is not identical to that of the truncated form of cystatin C deposited in hereditary cerebral hemorrhage with amyloidosis in Iceland (HCHWA-I), but that of normal cystatin C. DNA sequence analysis of five patients showed no point mutations in the cystatin C gene. Cystatin C and beta-protein colocalization, which was recognized in amyloid lesions of CAA, suggests that cystatin C deposition may be related to beta-protein deposition. We hypothesize that cystatin 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.
Nagai
A
A
Department of Internal Medicine III, Shimane Medical University, Izumo, Japan. nagaia@shimane-med.ac.jp
Kobayashi
S
S
Shimode
K
K
Imaoka
K
K
Umegae
N
N
Fujihara
S
S
Nakamura
M
M
D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D000682:Amyloid / Q000302:isolation & purification; D016229:Amyloid beta-Peptides / Q000032:analysis; D000818:Animals; D016657:Cerebral Amyloid Angiopathy / Q000134:cerebrospinal fluid / Q000235:genetics*; D055316:Cystatin C; D015891:Cystatins / Q000134:cerebrospinal fluid / Q000235:genetics*; D015853:Cysteine Proteinase Inhibitors / Q000134:cerebrospinal fluid / Q000235:genetics; D005260:Female; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007930:Leucine / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017354:Point Mutation
D000682:Amyloid; D016229:Amyloid beta-Peptides; C525030:CST3 protein, human; C525031:Cst3 protein, mouse; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D005973:Glutamine; D007930:Leucine