On the role of monocytes/macrophages in the pathogenesis of central nervous system lesions in hereditary cystatin C amyloid angiopathy

Leifur Thorsteinsson*, Gudmundur Georgsson, Bjarni Ásgeirsson, María Bjarnadóttir, Ísleifur Ólafsson, Ólafur Jensson, Gunnar Gudmundsson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


The pathogenesis of the deposition of a variant cystatin C as amyloid in hereditary cystatin C amyloid angiopathy (HCCAA) is not known. To address this question the synthesis and secretion of cystatin C in cultured monocytes from 9 carriers of the mutated cystatin C gene (5 symptomatic and 4 asymptomatic) was examined. The quantity of cystatin C in cells and supernatants was determined by the ELISA method, Western blots were done and selected samples immunostained for cystatin C. Monocytes from individuals carrying the gene defect synthesized cystatin C that was apparently not truncated, a form found in the cerebral amyloid deposits in HCCAA, but showed a distinctly lower rate of cystatin C synthesis than monocytes from healthy controls. The main difference was that the quantity of cystatin C was significantly lower in the supernatants in monocyte cultures from carriers of the gene defect than from healthy controls, possibly due to a partial block in its secretion. This abnormal processing of the cystatin C could explain the low cerebrospinal fluid levels of cystatin C in HCCAA and might be a part of the pathogenetic pathway of amyloid deposition. Furthermore it could, through a lower extracellular concentration of this inhibitor of cysteine proteinases, contribute to destruction of the amyloidotic blood vessels, leading to the most serious clinical manifestation in HCCAA, intracerebral hemorrhage.

Original languageEnglish
Pages (from-to)121-128
Number of pages8
JournalJournal of the Neurological Sciences
Issue number2
Publication statusPublished - Apr 1992

Bibliographical note

Funding Information:
G|sli Hreinsson for help with preparation of the manuscript. This work was supported by a grant from The Icelandic Council for Sciences, Heilavernd Society, the Blood Donor Society of Iceland, The B. Magn~sd6ttir and J.J. Bjaruason Foundation and the Medical Faculty at the University of Lund, Sweden. Part of this work was presented at the VIth International Symposium on Amyloidosis,

Other keywords

  • Cystatin C
  • Hereditary amyloid angiopathy
  • Intracerebral hemorrhage
  • Monocytes
  • Pathogenesis


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