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Gerstmann-Sträussler-Scheinker disease showing β-protein type cerebellar and cerebral amyloid angiopathy

Abstract

Cerebral amyloid angiopathy is observed in several brain degenerative disorders, but this pathological condition has received little attention in Gerstmann-Sträussler-Scheinker disease (GSS). We report a 69-year-old man who showed the cardinal features of GSS together with typical and extensive congophilic angiopathy. Immunohistochemical studies revealed that the vast majority of the amyloid plaques present in the brain of this patient were consistently labeled by anti-prion protein (PrP) antibody. Double immunostaining disclosed many additional β-protein immunoreactive plaque-like lesions, including a special type of “hybrid” plaque with colocalization of PrP and β-protein (β-PrP). The vascular amyloid deposits seen in both the cerebellum and cerebrum were immunoreactive only to anti-β-protein antibody. It seems likely that the extensive deposition of β-protein amyloid (including brain vascular amyloidosis) seen in this and other similar cases is part of pathology of GSS, although the possibility that this finding is due to ageing or concomitant Alzheimer's disease cannot be completely ruled out.

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References

  1. 1.

    Allsop D, Landon M, Kidd M, Lowe JS, Reynolds GP, Gardner A (1986) Monoclonal antibody raised against a subsequence of senile plaque core protein react with plaque cores, plaque periphery and cerebrovascular amyloid in Alzheimer's disease. Neurosci Lett 68: 252–256

  2. 2.

    Allsop D, Ikeda S, Bruce ME, Glenner GG (1988) Cerebrovascular amyloid in scrapie-affected sheep reacts with antibodies to prion protein. Neurosci Lett 92: 234–239

  3. 3.

    Amano N, Yagishita S, Yokoi S, Itoh Y, Kinoshita J, Mizutani T, Matsushita T (1992) Gerstmann-Sträussler syndrome — A variant type: amyloid plaques and Alzheimer's neurofibrillary tangles in cerebral cortex. Acta Neuropathol 84: 15–23

  4. 4.

    Bruce ME, McBride PA, Farquhar CF (1989) Precise targeting of the pathology of the sialoglycoprotein, PrP, and vacuolar degeneration in mouse scrapie. Neurosci Lett 102: 1–6

  5. 5.

    Bugiani O, Giaccone G, Verga L, Pollo B, Frangione B, Farlow MR, Tagliavini F, Ghetti B (1993) β-PP participates in PrP-amyloid plaques of Gerstmann-Sträussler-Scheinker disease, Indiana kindred. J Neuropathol Exp Neurol 52: 64–70

  6. 6.

    Davies L, Wolska B, Hilbich C, Multhaup G, Martins R, Simms G, Beyreuther K, Masters CL (1988) A4 amyloid protein deposition and the diagnosis of Alzheimer's disease: prevalence in aged brains determined by immunocytochemistry compared with conventional neuropathological techniques. Neurology 38: 1688–1693

  7. 7.

    DeArmond SJ, McKinley MP, Barry RA, Braunfeld MB, McColloch JR, Prusiner SB (1985) Identification of prion amyloid filaments in scrapie-infected brain. Cell 41: 221–235

  8. 8.

    De Courten-Myers G, Mandybur TI (1987) Atypical Gerstmann-Sträussler syndrome or familial spinocerebellar ataxia and Alzheimer's disease? Neurology 37: 269–275

  9. 9.

    Dlouhy SR, Hsiao K, Farlow MR, Foround T, Conneally PM, Johnson P, Prusiner SB, Hodes ME, Ghetti B (1992) Linkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease due to the prion protein gene. Nature Genet 1: 64–67

  10. 10.

    Doh-ura K, Tateishi J, Sasaki H, Kitamoto T, Sakaki Y (1989) Pro Leu change at position 102 of prion protein is the most common but not the sole mutation related to Gerstmann-Sträussler syndrome. Biochem Biophys Res Commun 163: 974–979

  11. 11.

    Ghetti B, Tagliavini F, Masters CL, Beyreuther K, Giaccone G, Verga L, Farlow MR, Conneally PM, Dlouhy SR, Azzarelli B, Bugiani O (1989) Gerstmann-Sträussler-Scheinker disease. II. Neurofibrillary tangles and plaques with PrP-amyloid coexist in an affected family. Neurology 39: 1453–1461

  12. 12.

    Gilmour JS, Bruce ME, MacKellar A (1986) Cerebrovascular amyloidosis in scrapie-affected sheep. Neuropathol Appl Neurobiol 12: 173–183

  13. 13.

    Glenner GG, Wong CW (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120: 885–890

  14. 14.

    Goldfarb LG, Brown P, Vrbovska A, Baron H, McCombie WR, Cathala F, Gibbs CJ, Gajdusek DC (1992) An insert mutation in the chromosome 20 amyloid precursor gene in a Gerstmann-Sträussler-Scheinker family. J Neurol Sci 111: 189–194

  15. 15.

    Hart J, Gordon B (1990) Early-onset dementia and extrapyramidal disease: clinicopathological variant of Gerstmann-Sträussler-Scheinker or Alzheimer's disease. J Neurol Neurosurg Psychiatry 53: 932–934

  16. 16.

    Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F, Terwilliger JD, Westaway D, Ott J, Prusiner SB (1989) Linkage of a prion protein missense variant to Gerstmann-Sträussler syndrome. Nature 338: 342–345

  17. 17.

    Hsiao K, Cass C, Schellenberg GD, Bird T, Devine-Gage E, Wisniewski H, Prusiner SB (1991) A prion protein variant in a family with the telencephalic form of Gerstmann-Sträussler-Scheinker syndrome. Neurology 41: 681–684

  18. 18.

    Hsiao K, Dlouhy SR, Farlow MR, Cass C, Costa MD, Conneally PM, Hodes ME, Ghetti B, Prusiner SB (1992) Mutant prion proteins in Gerstmann-Sträussler-Scheinker disease with neurofibrillary tangles. Nature Genet 1: 68–71

  19. 19.

    Ihara Y (1988) Massive somatodendritic sprouting of cortical neurons in Alzheimer's disease. Brain Res 459: 138–144

  20. 20.

    Ikeda S, Allsop D, Glenner GG (1989) Morphology and distribution of plaques and related deposits. An immunohistochemical study using amyloid β-protein antibody. Lab Invest 60: 113–122

  21. 21.

    Ikeda S, Yanagisawa N, Allsop D, Glenner GG (1990) Early senile plaques in Alzheimer's disease demonstrated by histochemistry, immunocytochemistry and electron microscopy. Hum Pathol 21: 1221–1226

  22. 22.

    Ikeda S, Yanagisawa N, Glenner GG, Allsop D (1992) Gerstmann-Sträussler-Scheinker disease showing β-protein amyloid deposits in the peripheral regions of PrP-immunoreactive amyloid plaques. Neurodegeneration 1: 281–288

  23. 23.

    Joachim CL, Morris JH, Kosik KS, Selkoe DJ (1987) Tau antisera recognize neurofibrillary tangles in a range of neurodegenerative disorders. Ann Neurol 22: 514–520

  24. 24.

    Kitamoto T, Tateishi J, Sato Y (1988) Immunohistochemical verification of senile and kuru plaques in Creutzfeldt-Jakob disease and the allied disease. Ann Neurol 24: 537–542

  25. 25.

    Masters CL, Gajdusek C, Gibbs CJ (1981) Creutzfeldt-Jakob disease virus isolation from the Gerstmann-Sträussler syndrome. With an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathies. Brain 104: 559–588

  26. 26.

    Miyazono M, Kitamoto T, Iwaki T, Tateishi J (1992) Colocalization of prion protein and β-protein in the same amyloid plaques in patients with Gerstmann-Sträussler-Scheinker syndrome. Acta Neuropathol 83: 333–339

  27. 27.

    Nakayama J, Katsuyama T, Sugiyama E, Hirabayashi Y (1993) Polysialosyl glycoconjugates defined by a monoclonal antibody M6704 are expressed in human glioma and embryonic neurons. J Histochem Cytochem 41: 1563–1572

  28. 28.

    Prusiner SB (1991) Molecular biology of prion diseases. Science 252: 1515–1522

  29. 29.

    Roberts GW, Lofthouse R, Allson D, Landon M, Kidd M, Prusiner SB, Crow TJ (1988) CNS amyloid proteins in neurodegenerative disease. Neurology 38: 1534–1540

  30. 30.

    Tateishi J, Kitamoto T, Doh-ura K, Boellaard JW, Peiffer J (1992) Creutzfeldt-Jakob disease with amyloid angiopathy: diagnosis by immunological analyses and transmission experiments. Acta Neuropathol 83: 559–563

  31. 31.

    Yamada M, Itoh Y, Fujigasaki H, Naruse S, Kaneko K, Kitamoto T, Tateishi J, Otomo E, Hayakawa M, Tanaka J, Matsushita M, Miyatake T (1993) A missense mutation at codon 105 with codon 129 polymorphism of the prion protein gene in a new variant of Gerstmann-Sträussler-Scheinker disease. Neurology 43: 2723–2724

  32. 32.

    Yamaguchi H, Hirai S, Morimatsu M, Shoji M, Ihara Y (1988) A variety of cerebral amyloid deposits in the brains of Alzheimer-type dementia demonstrated by β-protein immunostaining. Acta Neuropathol 76: 541–549

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Author information

Correspondence to Shu-ichi Ikeda.

Additional information

Supported by a research grant from the Intractable Disease Division, Ministry of Health and Welfare, Primary Amyloidosis Research Committee, Japan

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Ikeda, S., Yanagisawa, N., Allsop, D. et al. Gerstmann-Sträussler-Scheinker disease showing β-protein type cerebellar and cerebral amyloid angiopathy. Acta Neuropathol 88, 262–266 (1994). https://doi.org/10.1007/BF00293403

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Key words

  • Gerstmann-Sträussler-Scheinker disease Alzheimer's disease
  • Amyloid
  • Amyloid angiopathy Prion protein