C and Cerebral Hemorrhage

Cystatin C amyloid deposits have been demonstrated to be associated with two types of brain hemorrhage. One type is the dominantly inherited form of cerebral hemorrhage, which is caused by a mutation in the cystatin C gene and displays amyloid deposition of the cystatin C variant but no co-deposition of amyloid (3-protein. The other type comprises the cerebral hemorrhage conditions, which are connected with cerebral deposition of amyloid (3-protein and display co-deposition of wildtype cystatin C in the amyloid. 

When HCCAA is suspected because of clinical observations and/or family history, the diagnosis can easily be verified by demonstrating a low cerebrospinal fluid level of cystatin C (G10, J3) or the presence of the mutated cystatin C allele producing the Leu 68 Gin cystatin C variant (A6, PI). The first-mentioned procedure requires lumbar puncture and, to secure a stable level of cystatin C in the sample, the addition of a serine protease inhibitor, e.g., benzamidinium chloride, directly when the sample is drawn (Grubb, A., unpublished results). The PCR-based procedure is more robust, does not require lumbar puncture, and can be used for prenatal diagnosis and is therefore presently the preferable diagnostic method. 

Cystatin C and Cerebral Hemorrhage Conditions Connected with Deposition of Amyloid (3-Protein 

The author s work described in this discourse was supported by the Swedish Medical Research Council (project 5196) and by A. Osterlund s, A. Pahlsson s, and G. and J. Kock s Foundations. 

Abrahamson, M., Barrett, A. J., Salvesen, G., and Grubb, A., Isolation of six cysteine proteinase inhibitors from human urine. Their physicochemical and enzyme kinetic properties and concentrations in biological fluids. J. Biol. Chem. 261(24), 11282—11289 (1986). 

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