The amino terminal portion of cerebrospinal fluid cystatin C in hereditary cystatin C amyloid angiopathy is not truncated: Direct sequence analysis from agarose gel electropherograms

I. Olafsson*, G. Gudmundsson, M. Abrahamson, O. Jensson, A. Grubb

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

The isolated amyloid substance in hereditary cystatin C amyloid angiopathy (HCCAA) is mainly composed of a cystatin C variant devoid of the 10 amino terminal amino acid residues of extracellular cystatin C from healthy individuals. We have developed a procedure for protein sequencing directly from agarose gel electropherograms and used this in conjunction with isoelectric focusing to investigate the amino terminal sequence of cerebrospinal fluid (CSF) cystatin C in HCCAA patients. The amino-terminal sequence determined for cystatin C from a HCCAA patient CSF sample, Xaa-Ser-Pro-Gly-Lys-Pro-Pro-Xaa-Leu-Val-Gly-Gly-Pro-Met-Xaa-Ala-Xaa-Val, showed that the protein was not amino-termi-nally truncated. CSF cystatin C from all nine HCCAA patients investigated was found to have an isoelectric point identical to that of native cystatin C., and the truncated form of cystatin C isolated from amyloid deposits was shown to contribute to less than 1 % of the total amount of cystatin C in CSF. The total cysteine proteinase inhibitory capacity of CSF from HCCAA patients was lower than that of CSF from other patients. This decreased CSF inhibitory capacity in HCCAA patients was caused by decreased levels of cystatin C., since the levels of the other two cysteine proteinase inhibitors found in CSF, α2-macroglobulin and kininogen, were significantly higher than in CSF from non-HCCAA patients.

Original languageEnglish
Pages (from-to)85-93
Number of pages9
JournalScandinavian Journal of Clinical and Laboratory Investigation
Volume50
Issue number1
DOIs
Publication statusPublished - Jan 1990

Bibliographical note

Funding Information:
This work was supported by the Heilavernd Society, The Icelandic Science Foundation, The B. Magnusdottir and J.J. Bjarnason Foundation, A. Osterlunds Stiftelse, Direktor A. PAhlssons Stiftelse, G. och J. Kocks Stiftelse, Konung Gustav V's 80-&-sfond, the Medical Faculty of the University of Lund and the Swedish Medical Research Council (project no. 05196).

Other keywords

  • agarose gel electrophoresis
  • amino acid sequence analysis
  • amyloidosis
  • cerebral haemorrhage
  • cystatin C
  • cysteine proteinase inhibitor

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