Advertisement

Distribution of Cystatin C Amyloid Deposits in the Icelandic Patients with Hereditary Cystatin C Amyloid Angiopathy

  • Leifur Thorsteinsson
  • Hannes Blöndal
  • Olafur Jensson
  • Gunnar Gudmundsson
Chapter

Abstract

Cystatin C, a basic microprotein inhibitor of lysosomal proteinases is a precursor of the amyloid fibril deposition in patients with hereditary cystatin C amyloid angiopathy (HCCAA) in Iceland. Cystatin C amyloid deposits were demonstrated immunohistochemically in the following areas. Firstly within the CNS in practically all arteries and arterioles throughout the CNS. Massive cystatin C amyloid was also present in interstitial tissue of the basal ganglia and the hippocampus, especially perivascularly. Spinal pia mater showed positive immuno-staining in all cases as did frequently the arachnoid and arachnoid granulations. Secondly, outside the CNS cystatin C amyloid deposits were demonstrated in the walls of small arteries in all lymphnodes investigated independent of localization in the body. Amyloid material was also detected in the inter-lobular connective tissue of the submandibular salivary gland. These findings suggest that the diagnosis of HCCAA can now be supported by two laboratory methods: Estimation of cystatin C in the cerebrospinal fluid and immunohistochemical study of lymphnode biopsies.

Keywords

Submandibular Salivary Gland Amyloid Deposit Amyloid Fibril Superior Sagittal Sinus Arachnoid Granulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    O. Jensson, G. Gudmundsson, A. Arnason, H. Blöndal, I. Petursdottir, L. Thorsteinsson, A. Grubb, H. Löfberg, D. Cohen and B. Frangione, Hereditary cystatin C (y-trace) amyloid angiopathy of the CNS causing cerebral hemorrhage, Acta Neurol. Scand. 76: 102 (1987).CrossRefGoogle Scholar
  2. 2.
    D.H. Cohen, H. Feiner, O. Jensson and B. Frangione, Amyloid fibril in hereditary cerebral hemorrhage with amyloidosis (HCHWA) is related to the gastroenteropancreatic neuro-endocrine protein, gamma trace, J. Exp. Med. 158: 623 (1983).CrossRefGoogle Scholar
  3. 3.
    H. Löfberg, A.O. Grubb, E.K. Nilsson, O. Jensson, G. Gudmundsson, H. Blöndal, A. Arnason and L. Thorsteinsson, Immunohistochemical characterization of the amyloid deposits and quantitation of pertinent cerebrospinal fluid proteins in hereditary cerebral hemorrhage with amyloidosis, Stroke 18: 431 (1987).CrossRefGoogle Scholar
  4. 4.
    A. Grubb, O. Jensson, G. Gudmundsson, A. Arnason, H. Löfberg and J. Malm, Abnormal metabolism of γ-trace alkaline microprotein. The basic defect in hereditary cerebral hemorrhage with amyloidosis, New Engl.J. Med. 311: 1547 (1984).CrossRefGoogle Scholar
  5. 5.
    O. Jensson, L. Thorsteinsson, A. Palsdottir, G. Gudmundsson, A. Arnason, H. Blöndal, M. Abrahamson, A. Grubb, I. Olafsson and A. Lundwall, An isolate of families with hereditary cystatin C amyloid angiopathy and cerebral hemorrhage in the South of Iceland, in this volume.Google Scholar
  6. 6.
    A. Grubb, V. Grimsberg and A. Grubb, Survey of the biochemistry and clinical chemistry of cystatin C alias γ-trace, Acta Neurol. Scand. 73: 309 (1986).Google Scholar
  7. 7.
    J. Ghiso, O. Jensson and B. Frangione, Amyloid fibril in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant γ-trace basic protein (cystatin C), Proc. Natl. Acad. Sci. 83: 2974 (1986).CrossRefGoogle Scholar
  8. 8.
    A. Palsdottir, O. Jensson, G. Gudmundsson, A. Arnason, M. Abrahamson, A. Grubb, I. Olafsson and A. Lundwall, Hereditary cystatin C amyloid angiopathy (HCCAA) with cerebral hemorrhage is not tightly linked to the cystatin C gene, in this volume.Google Scholar
  9. 9.
    G.M. Hochwald and G.J. Thorbecke, Abnormal metabolism or reduced transport of CSF γ-trace microprotein hereditary cerebral hemorrhage with amyloidosis, New Engl. J. Med. 312: 1127 (1985).Google Scholar
  10. 10.
    H. Löfberg, A.O. Grubb and A. Brun, Human brain cortical neurons contain γ-trace. Rapid isolation, immunohistochemical and physiochemical characterization of human γ-trace, Biomed. Res. 2: 298 (1981).Google Scholar
  11. 11.
    R.J. Davies, R.B. North, J.N. Cambell and R.A. Suss, Multiple cerebral hemorrhages following chymopapin chemonucleolysis, J. Neurosurg. 61: 169 (1984)CrossRefGoogle Scholar
  12. 12.
    P.J. Garvin, R.B. Jennings, L. Smith and R.M. Gesler, Chymopapin: A pharmacologic and toxiologic evaluation in experimental animals, Clin. Orthop. 41: 204 (1965).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Leifur Thorsteinsson
    • 1
  • Hannes Blöndal
    • 2
  • Olafur Jensson
    • 1
  • Gunnar Gudmundsson
    • 3
  1. 1.The Blood Bank, Genetic DivisionUniversity of Iceland, National HospitalReykjavikUSA
  2. 2.Departments of Anatomy and PathologyUniversity of Iceland, National HospitalReykjavikUSA
  3. 3.Department of NeurologyUniversity of Iceland, National HospitalReykjavikUSA

Personalised recommendations