No mutations in cystatin C gene in cerebral amyloid angiopathy with cystatin C deposition.

Abstract

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.

• Authors: A Nagai, S Kobayashi, K Shimode, K Imaoka, N Umegae, S Fujihara, M Nakamura
• Journal: Molecular and chemical neuropathology (Mol Chem Neuropathol) Vol. 33 Issue 1 Pg. 63-78 (Jan 1998) ISSN: 1044-7393 [Print] United States
• PMID: 9493177 (Publication Type: Case Reports, Journal Article)

Chemical References

• Amyloid
• Amyloid beta-Peptides
• CST3 protein, human
• Cst3 protein, mouse
• Cystatin C
• Cystatins
• Cysteine Proteinase Inhibitors
• Glutamine
• Leucine

Topics

• Aged
• Amino Acid Substitution (genetics)
• Amyloid (isolation & purification)
• Amyloid beta-Peptides (analysis)
• Animals
• Cerebral Amyloid Angiopathy (cerebrospinal fluid, genetics)
• Cystatin C
• Cystatins (cerebrospinal fluid, genetics)
• Cysteine Proteinase Inhibitors (cerebrospinal fluid, genetics)
• Female
• Glutamine (genetics)
• Humans
• Immunohistochemistry
• Leucine (genetics)
• Male
• Mice
• Mice, Inbred BALB C
• Point Mutation