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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1995 Jun;58(6):699–705. doi: 10.1136/jnnp.58.6.699

Hereditary cerebral haemorrhage with amyloidosis, Dutch type (HCHWA-D): clinicopathological studies.

A R Wattendorff 1, B Frangione 1, W Luyendijk 1, G T Bots 1
PMCID: PMC1073548  PMID: 7608669

Abstract

Clinical and neuropathological findings are reported in 63 patients with hereditary cerebral haemorrhage with amyloid angiopathy. Patients had mostly recurrent strokes, and at least 80% of these were haemorrhages. Almost a third of the patients died within a year of their first and only recorded haemorrhage, half of them within two weeks. This angiopathy was restricted to the cerebral and cerebellar cortex and its covering leptomeninges. As the most important consequence, haemorrhagic infarcts and haemorrhages occurred in the subcortical white matter--that is, the region most vulnerable to impaired cortical circulation. Further development of these subcortical lesions gives rise to the fatal haemorrhages seen at necropsy. In so far as dementia occurs this is likely to result from multiple microinfarcts or haemorrhages. In most cases preamyloid lesions or diffuse plaques and early plaques were seen. No other type of plaque or neurofibrillary degeneration was found. The plaques occur in conjunction with the angiopathy, but may not occur even when the angiopathy is severe. In one patient plaques were totally absent. Angiopathy and plaques may be the result of the same mutation, the expression of which is governed by tissue factors or phenotypic differences between individual subjects.

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Selected References

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  1. Cohen D. H., Feiner H., Jensson O., Frangione B. Amyloid fibril in hereditary cerebral hemorrhage with amyloidosis (HCHWA) is related to the gastroentero-pancreatic neuroendocrine protein, gamma trace. J Exp Med. 1983 Aug 1;158(2):623–628. doi: 10.1084/jem.158.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Coria F., Castaño E. M., Frangione B. Brain amyloid in normal aging and cerebral amyloid angiopathy is antigenically related to Alzheimer's disease beta-protein. Am J Pathol. 1987 Dec;129(3):422–428. [PMC free article] [PubMed] [Google Scholar]
  3. Coria F., Prelli F., Castaño E. M., Larrondo-Lillo M., Fernandez-Gonzalez J., van Duinen S. G., Bots G. T., Luyendijk W., Shelanski M. L., Frangione B. Beta-protein deposition: a pathogenetic link between Alzheimer's disease and cerebral amyloid angiopathies. Brain Res. 1988 Oct 25;463(1):187–191. doi: 10.1016/0006-8993(88)90545-8. [DOI] [PubMed] [Google Scholar]
  4. Eikelenboom P., Stam F. C. An immunohistochemical study on cerebral vascular and senile plaque amyloid in Alzheimer's dementia. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;47(1):17–25. doi: 10.1007/BF02890185. [DOI] [PubMed] [Google Scholar]
  5. Ghiso J., Jensson O., Frangione B. Amyloid fibrils in hereditary cerebral hemorrhage with amyloidosis of Icelandic type is a variant of gamma-trace basic protein (cystatin C). Proc Natl Acad Sci U S A. 1986 May;83(9):2974–2978. doi: 10.1073/pnas.83.9.2974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Glenner G. G., Wong C. W. Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1131–1135. doi: 10.1016/0006-291x(84)91209-9. [DOI] [PubMed] [Google Scholar]
  7. Gudmundsson G., Hallgrímsson J., Jónasson T. A., Bjarnason O. Hereditary cerebral haemorrhage with amyloidosis. Brain. 1972;95(2):387–404. doi: 10.1093/brain/95.2.387. [DOI] [PubMed] [Google Scholar]
  8. Haan J., Lanser J. B., Zijderveld I., van der Does I. G., Roos R. A. Dementia in hereditary cerebral hemorrhage with amyloidosis-Dutch type. Arch Neurol. 1990 Sep;47(9):965–967. doi: 10.1001/archneur.1990.00530090035010. [DOI] [PubMed] [Google Scholar]
  9. Haan J., Roos R. A. Coexistence of cystatin C and beta protein immunoreactivity. Stroke. 1990 Oct;21(10):1510–1510. [PubMed] [Google Scholar]
  10. Hart M. N., Merz P., Bennett-Gray J., Menezes A. H., Goeken J. A., Schelper R. L., Wisniewski H. M. beta-amyloid protein of Alzheimer's disease is found in cerebral and spinal cord vascular malformations. Am J Pathol. 1988 Jul;132(1):167–172. [PMC free article] [PubMed] [Google Scholar]
  11. Julien J., Vital C., Lagueny A., Ferrer X., Vital A. Hémorragie cérébrale récidivante et angiopathie amyloïde. Rev Neurol (Paris) 1983;139(12):763–767. [PubMed] [Google Scholar]
  12. Kitamoto T., Ogomori K., Tateishi J., Prusiner S. B. Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids. Lab Invest. 1987 Aug;57(2):230–236. [PubMed] [Google Scholar]
  13. LUYENDIJK W., SCHOEN J. H. INTRACEREBRAL HEMATOMAS. A CLINICAL STUDY OF 40 SURGICAL CASES. Psychiatr Neurol Neurochir. 1964 Nov-Dec;67:445–468. [PubMed] [Google Scholar]
  14. Leblanc R., Preul M., Robitaille Y., Villemure J. G., Pokrupa R. Surgical considerations in cerebral amyloid angiopathy. Neurosurgery. 1991 Nov;29(5):712–718. doi: 10.1097/00006123-199111000-00012. [DOI] [PubMed] [Google Scholar]
  15. Levy E., Carman M. D., Fernandez-Madrid I. J., Power M. D., Lieberburg I., van Duinen S. G., Bots G. T., Luyendijk W., Frangione B. Mutation of the Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science. 1990 Jun 1;248(4959):1124–1126. doi: 10.1126/science.2111584. [DOI] [PubMed] [Google Scholar]
  16. Luyendijk W., Bots G. T., Vegter-van der Vlis M., Went L. N., Frangione B. Hereditary cerebral haemorrhage caused by cortical amyloid angiopathy. J Neurol Sci. 1988 Jul;85(3):267–280. doi: 10.1016/0022-510x(88)90186-4. [DOI] [PubMed] [Google Scholar]
  17. Mandybur T. I. The incidence of cerebral amyloid angiopathy in Alzheimer's disease. Neurology. 1975 Feb;25(2):120–126. doi: 10.1212/wnl.25.2.120. [DOI] [PubMed] [Google Scholar]
  18. Michel B., Gastaut J. L., Gambarelli D., Chave B. Hématomes intracérébraux lobaires récidivants au cours de l'angiopathie amyloïde cérébrale. Un cas clinico-pathologique. Rev Neurol (Paris) 1988;144(8-9):503–507. [PubMed] [Google Scholar]
  19. Palsdottir A., Abrahamson M., Thorsteinsson L., Arnason A., Olafsson I., Grubb A., Jensson O. Mutation in cystatin C gene causes hereditary brain haemorrhage. Lancet. 1988 Sep 10;2(8611):603–604. doi: 10.1016/s0140-6736(88)90641-1. [DOI] [PubMed] [Google Scholar]
  20. Pardridge W. M., Vinters H. V., Yang J., Eisenberg J., Choi T. B., Tourtellotte W. W., Huebner V., Shively J. E. Amyloid angiopathy of Alzheimer's disease: amino acid composition and partial sequence of a 4,200-dalton peptide isolated from cortical microvessels. J Neurochem. 1987 Nov;49(5):1394–1401. doi: 10.1111/j.1471-4159.1987.tb01005.x. [DOI] [PubMed] [Google Scholar]
  21. Rozemuller A. J., Roos R. A., Bots G. T., Kamphorst W., Eikelenboom P., Van Nostrand W. E. Distribution of beta/A4 protein and amyloid precursor protein in hereditary cerebral hemorrhage with amyloidosis-Dutch type and Alzheimer's disease. Am J Pathol. 1993 May;142(5):1449–1457. [PMC free article] [PubMed] [Google Scholar]
  22. Selkoe D. J. The molecular pathology of Alzheimer's disease. Neuron. 1991 Apr;6(4):487–498. doi: 10.1016/0896-6273(91)90052-2. [DOI] [PubMed] [Google Scholar]
  23. Torack R. M. Congophilic angiopathy complicated by surgery and massive hemorrhage. A light and electron microscopic study. Am J Pathol. 1975 Nov;81(2):349–366. [PMC free article] [PubMed] [Google Scholar]
  24. Vinters H. V. Cerebral amyloid angiopathy. A critical review. Stroke. 1987 Mar-Apr;18(2):311–324. doi: 10.1161/01.str.18.2.311. [DOI] [PubMed] [Google Scholar]
  25. Vinters H. V., Secor D. L., Pardridge W. M., Gray F. Immunohistochemical study of cerebral amyloid angiopathy. III. Widespread Alzheimer A4 peptide in cerebral microvessel walls colocalizes with gamma trace in patients with leukoencephalopathy. Ann Neurol. 1990 Jul;28(1):34–42. doi: 10.1002/ana.410280108. [DOI] [PubMed] [Google Scholar]
  26. Wattendorff A. R., Bots G. T., Went L. N., Endtz L. J. Familial cerebral amyloid angiopathy presenting as recurrent cerebral haemorrhage. J Neurol Sci. 1982 Aug;55(2):121–135. doi: 10.1016/0022-510x(82)90094-6. [DOI] [PubMed] [Google Scholar]
  27. Wong C. W., Quaranta V., Glenner G. G. Neuritic plaques and cerebrovascular amyloid in Alzheimer disease are antigenically related. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8729–8732. doi: 10.1073/pnas.82.24.8729. [DOI] [PMC free article] [PubMed] [Google Scholar]

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