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The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids

Bjarnadottir, M.; Nilsson, C.; Lindström, Veronica LU ; Westman, A.; Davidsson, P.; Thormodsson, F.; Blondal, H.; Gudmundsson, G. and Grubb, A. (2001) In Amyloid 8(1). p.41284-41284
Abstract
A variant of the normal extracellular cysteine protease inhibitor cystatin C (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid angiopathy (HCCAA). It has been suggested that the mutation causes cellular entrapment of L68Q-cystatin C in vivo and that the variant protein is not secreted to extracellular fluids. In order to test this hypothesis, we used matrix-assisted laser desorption ionization time-of-flight mass spectrometry in an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in plasma and cerebrospinal fluid (CSF) of HCCAA-patients. Plasma from all five investigated HCCAA-patients contained both L68Q- and wildtype cystatin C. The presence of approximately equal amounts of cystatin C... (More)
A variant of the normal extracellular cysteine protease inhibitor cystatin C (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid angiopathy (HCCAA). It has been suggested that the mutation causes cellular entrapment of L68Q-cystatin C in vivo and that the variant protein is not secreted to extracellular fluids. In order to test this hypothesis, we used matrix-assisted laser desorption ionization time-of-flight mass spectrometry in an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in plasma and cerebrospinal fluid (CSF) of HCCAA-patients. Plasma from all five investigated HCCAA-patients contained both L68Q- and wildtype cystatin C. The presence of approximately equal amounts of cystatin C dimers and monomers was demonstrated in plasma from HCCAA-patients, whereas only monomers could be found in normal plasma. L68Q-wildtype-cystatin C heterodimers seem to be present in the dimeric cystatin C population. CSF from six HCCAA-patients also contained cystatin C-dimers and monomers, bur the dimeric fraction was minute. CSF from control patients did not contain dimeric cystatin C. These results suggest that the milieu of L68Q-cystatin C is important for its stability and dimerization status and that certain milieus might hinder its further development into oligomers, amyloid fibrils and other precipiting aggregates. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Amyloid
volume
8
issue
1
pages
41284 - 41284
publisher
Parthenon Publishing
external identifiers
  • wos:000169107300001
  • scopus:0035093468
ISSN
1350-6129
language
English
LU publication?
yes
id
5ada0d3c-0bc6-4072-ae7d-bec9c66305cf (old id 1119177)
date added to LUP
2008-06-25 09:57:54
date last changed
2018-06-24 04:35:26
@article{5ada0d3c-0bc6-4072-ae7d-bec9c66305cf,
  abstract     = {A variant of the normal extracellular cysteine protease inhibitor cystatin C (L68Q-cystatin C), is the amyloid precursor in hereditary cystatin C amyloid angiopathy (HCCAA). It has been suggested that the mutation causes cellular entrapment of L68Q-cystatin C in vivo and that the variant protein is not secreted to extracellular fluids. In order to test this hypothesis, we used matrix-assisted laser desorption ionization time-of-flight mass spectrometry in an effort to demonstrate the presence of L68Q- along with wildtype cystatin C in plasma and cerebrospinal fluid (CSF) of HCCAA-patients. Plasma from all five investigated HCCAA-patients contained both L68Q- and wildtype cystatin C. The presence of approximately equal amounts of cystatin C dimers and monomers was demonstrated in plasma from HCCAA-patients, whereas only monomers could be found in normal plasma. L68Q-wildtype-cystatin C heterodimers seem to be present in the dimeric cystatin C population. CSF from six HCCAA-patients also contained cystatin C-dimers and monomers, bur the dimeric fraction was minute. CSF from control patients did not contain dimeric cystatin C. These results suggest that the milieu of L68Q-cystatin C is important for its stability and dimerization status and that certain milieus might hinder its further development into oligomers, amyloid fibrils and other precipiting aggregates.},
  author       = {Bjarnadottir, M. and Nilsson, C. and Lindström, Veronica and Westman, A. and Davidsson, P. and Thormodsson, F. and Blondal, H. and Gudmundsson, G. and Grubb, A.},
  issn         = {1350-6129},
  language     = {eng},
  number       = {1},
  pages        = {41284--41284},
  publisher    = {Parthenon Publishing},
  series       = {Amyloid},
  title        = {The cerebral hemorrhage-producing cystatin C variant (L68Q) in extracellular fluids},
  volume       = {8},
  year         = {2001},
}