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Cited by 72Prion Diseases and Protein MisfoldingAlzheimer's disease research and treatmentsAmyloidosis: Diagnosis, Treatment, Outcomes

Ultrastructural study of florid plaques in variant Creutzfeldt–Jakob disease: a comparison with amyloid plaques in kuru, sporadic Creutzfeldt–Jakob disease and Gerstmann–Sträussler–Scheinker disease

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Sikorska, B., Liberski, P. P., Sobów, T., Budka, H., Ironside, J. W.·2009·Neuropathology and Applied Neurobiology
DOI 10.1111/j.1365-2990.2008.00959.x
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Abstract

Background: Although the histological features of the amyloid plaques in variant Creutzfeldt–Jakob disease (vCJD) are distinct from those in other forms of prion disease [kuru, sporadic Creutzfeldt–Jakob disease (sCJD) and Gerstmann–Sträussler–Scheinker disease (GSS)], their ultrastructural features have only been described in a single case report. Aims: To study vCJD plaques systematically and compare them with plaques in kuru, sCJD, GSS and Alzheimer disease (AD). Methods: Amyloid plaques were studied by transmission electron microscopy and image analysis in five cases of vCJD, three cases of GSS, two cases of sCJD, one case of kuru and five cases of AD. Immunohistochemistry was performed on paraffin sections from one case of vCJD, two cases of GSS, one case of kuru and two cases of sCJD. Results: The florid plaques in vCJD were either compact or more diffuse; in both forms, the radiating fibrils were organized into thick ‘tongues’, in contrast to kuru plaques. Dystrophic neurites (DNs) containing lysosomal electron‐dense bodies or vesicles surrounded florid plaques. Microglial cells were found within florid plaques; occasional amyloid fibrils were identified in membrane‐bound pockets of microglial cells. In vCJD, there was significant tau immunoreactivity in DNs around florid plaques while, in sCJD, GSS and kuru, minimal tau immunoreactivity was observed around plaques. Conclusions: The ultrastructure of the florid plaques and DNs in vCJD is more reminiscent of neuritic plaques in AD than kuru or multicentric plaques. These findings may reflect differences both in the strains of the transmissible agents responsible for these disorders and in host factors.

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  • The most striking neuropathologic feature of kuru is the presence of numerous amyloid plaques, known as kuru plaques.

    “The most striking neuropathologic feature of kuru is the presence of numerous amyloid plaques described as “spherical bodies with a rim of radiating filaments” and found in 6 of 12 cases studied by Klatzo et al (62) and in “about three quarters” of the 13 cases of Beck and Daniel (68); they then became known as “kuru plaques” (67, 69–71).”

    From Kuru (2012) · cites this paper as [71]

    The Introduction discusses kuru plaques, and the Results describe them as amyloid plaques with radiating fibrils. The paper does not establish that they are numerous in kuru or its most striking neuropathologic feature. The indexed passages provide section labels but no page numbers. (LLM, conf=0.83)

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  • The fine structure of amyloid plaques from the "K" case corresponds to that described by light microscopy.

    “The fine structure of plaques was surprisingly well preserved, and it corresponds to that described by light microscopy (71).”

    From Kuru (2012) · cites this paper as [71]

    The Introduction (page unavailable) says the authors compared plaques by light and electron microscopy and proposed that ultrastructural differences in vCJD are reflected in their light-microscopic appearance. The Methods confirm that they examined a kuru case, but the passages found do not say that the fine structure of plaques from the “K” case corresponded to its light-microscopic description or was surprisingly well preserved. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

  • In our previous study on amyloid plaques in prion diseases, we demonstrated that kuru plaques morphologically and ultrastructurally resemble those characteristic of sporadic CJD subtype 3 according to the Parchi and Gambetti classification but are remarkably different from florid plaques in variant CJD and multicentric plaques in GSS.

    “In our previous study on amyloid plaques encountered in prion diseases (71), we demonstrated that kuru plaques morphologically and ultrastructurally resemble those that are characteristic of sporadic CJD subtype 3 according to the Parchi and Gambetti classification (22) but were remarkably different from florid plaques in variant CJD and multicentric plaques in GSS.”

    From Kuru (2012) · cites this paper as [71]

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Research works printed but not linked: 48

  1. Gajdusek DC, Gibbs CJ, Alpers MP. Experimental trans- mission of a kuru-like syndrome to chimpanzees. Nature 1966; 209: 794-6
  2. Gibbs CJ Jr, Gajdusek DC, Asher DM, Alpers MP, Beck E, Daniel PM, Matthews WB. Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to chimpan- zee. Science 1968; 161: 388-9
  3. Masters CL, Gajdusek DC, Gibbs CJ Jr. Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Sträussler syndrome. With an analysis of the various forms of amyloid plaque deposition in the virus induced spongi- form encephalopathies. Brain 1981; 104: 559-88
  4. Hainfellner J, Brantner-Inhaler S, Cervenakova L, Brown P, Kitamoto T, Tateishi J, Diringer H, Liberski PP, Regele H, Feucht M, Mayr N, Wessely K, Summer K, Seitelberger F, Budka H. The original Gerstmann-Sträussler- Scheinker family of Austria: divergent clinicopathological phenotypes but constant PrP genotype. Brain Pathol 1995; 5: 201-13
  5. Collinge J, Palmer MS, Sidle KCL, Gowland I, Medori R, Ironside J, Lantos P. Transmission of fatal familial insomnia to laboratory animals. Lancet 1995; 346: 569-70
  6. Kimberlin RH, Marsh RF. Comparison of scrapie and transmissible mink encephalopathy in hamsters. I. Bio- chemical studies of brain during development of disease. J Infect Dis 1975; 131: 97-103
  7. Williams ES, Young S. Chronic wasting disease of captive mule deer: a spongiform encephalopathy. J Wildlife Dis 1980; 16: 89-98
  8. Williams ES, Young S. Spongiform encephalopathy of Rocky Mountain elk. J Wildlife Dis 1982; 18: 465- 71
  9. Liberski PP, Guiroy DC, Williams ES, Walis A, Budka H. Deposition patterns of disease-associated prion protein in captive mule deer brains with chronic wasting disease. Acta Neuropathol (Berl) 2001; 102: 496-500.
  10. Wells GAH, Scott AC, Johnson CT, Gunning RF, Hancock RD, Jeffrey M, Dawson M, Bradley R. A novel progressive spongiform encephalopathy in cattle. Vet Rec 1987; 121: 419-20 12
  11. Masters CL, Multhaup G, Simms G, Pottgiesser J, Martins RL, Beyreuther K. Neuronal origin of a celebrated amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 1985; 4: 2757-63 13
  12. Ghiso J, Vidal R, Rostagno A, Miravalle L, Holton JL, Mead S, Revesz T, Plant G, Frangione B. Amyloidogenesis in familial British dementia is associated with a genetic defect on chromosome 13. Ann N Y Acad Sci 2000; 920: 84-92
  13. Brown P, Goldfarb LG, Gajdusek DC. The new biology of spongiform encephalopathy: infectious amyloidoses with a genetic twist. Lancet 1991; 337: 1019-22
  14. Brown P, Brandel JP, Preece M, Sato T. Iatrogenic Creutzfeldt-Jakob disease: the waning era. Neurology 2006; 67: 389-93
  15. Will RG, Ironside JW, Zeidler M, Cousens SN, Estibeiro K, ALperovitch A, Poser S, Pocchari M, Hofman A, Smith PG. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 1996; 347: 921-5 18
  16. Parchi P, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H. Classification of sporadic Creutzfeldt- Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 1999; 46: 224-33 19
  17. Klatzo I, Gajusek DC. Pathology of kuru. Lab Invest 1959; 8: 799-847
  18. Hainfellner JA, Liberski PP, Guiroy DC, Cervenakova L, Brown P, Gajdusek DC, Budka H. Pathology and immu- nocytochemistry of a kuru brain. Brain Pathol 1997; 7: 547-54
  19. Ironside JW, Bell JB. Florid plaques and new variant Creutzfeldt-Jakob disease. Lancet 1997; 350: 1475
  20. Liberski PP, Budka H. Ultrastructural pathology of Gerstmann-Sträussler-Scheinker disease. Ultrastruct Pathol 1995; 19: 23-36
  21. Fraser H. The pathology of a natural and experimental scrapie. Front Biol 1976; 44: 267-305
  22. Casalone C, Zanusso G, Acutis P, Ferrari S, Capucci L, Tagliavini F, Monaco S, Caramelli M. Identification of a second bovine amyloidotic spongiform encephalopa- thy: molecular similarities with sporadic Creutzfeldt- Jakob disease. Proc Natl Acad Sci USA 2004; 101: 3065-70 25
  23. Fournier FG, Kopp N, Streichenberger N, Escaig-Haye F, Langeveld J, Brown P. Electron microsocopy of brain amyloid plaques from a patient with new variant Creutzfeldt-Jakob disease. Acta Neuropathol (Berl) 2000; 99: 637-42
  24. Boellaard JW, Doerr-Schott J, Schlote W. Miniplaques and shapeless cerebral amyloid deposits in a case of Gerstmann-Sträussler-Scheinker disease. Acta Neuro- pathol (Berl) 1993; 86: 532-5
  25. Brown P, Goldfarb LG, Brown WT, Goldgaber D, Ruben- stein R, Kascak RJ, Guiroy DC, Piccardo P, Boellaard JW, Gajdusek DC. Clinical and molecular genetic study of a large German kindred with Gerstmann-Sträussler- Scheinker syndrome. Neurology 1991; 41: 375-9
  26. Boellaard JW, Brown P, Tateishi J. Gerstmann-Sträussler- Scheinker disease -the dilemma of molecular and clinical correlations. Clin Neuropathol 1999; 18: 271- 85 29
  27. Budka H, Aguzzi A, Brown P, Brucher JM, Bugiani O, Gullotta F, Haltia M, Hauw J-J, Ironside JW, Jellinger K, Kretzschmar HA, Lantos PL, Masullo C, Schlote W, Tateishi J, Weller RO. Consensus report. Neuropathologi- cal diagnostic criteria for Creutzfeldt-Jakob disease (CJD) and other human spongiform encephalopathies (prion diseases). Brain Pathol 1995; 4: 459-66
  28. Alwasiak J, Mirecka B, Wozniak L, Liberski PP. Neuroblas- tic differentiation of metastases of medulloblastoma to extracranial lymph node: an ultrastructural study. Ultra- struct Pathol 1991; 15: 647-54
  29. Barcikowska M, Liberski PP, Boellaard J, Brown P, Gaj- dusek DC, Budka H. Microglia is a component of the prion protein amyloid plaque in the Gerstmann-Sträussler- Scheinker syndrome. Acta Neuropathol (Berl) 1993; 85: 623-7
  30. Liberski PP, Sikorska B, Bratosiewicz-Wasik J, Gajdusek DC, Brown P. Neuronal cell death in transmissible spongi- form encephalopathies (prion diseases) revisited: from apoptosis to autophagy. Int J Biochem Cell Biol 2004; 36: 2473-90
  31. Sikorska B, Liberski PP, Giraud P, Kopp N, Brown P. Autophagy is a part of ultrastructural synaptic pathology in Creutzfeldt-Jakob disease: a brain biopsy study. Int J Biochem Cel Biol 2004; 36: 2563-73
  32. Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, Cuervo AM. Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol 2005; 64: 113-22
  33. Wisniewski HM, Terry RD. Re-examination of the patho- genesis of the senile plaques. In Progress in Neuropathol- ogy Vol. 2. Ed. HM Zimmerman. New York: Grune & Stratton, 1973; 1-26
  34. Liberski PP, Brown P. Disease-specific particles without prion protein in prion diseases -phenomenon or epiphe- nomenon? Neuropathol Appl Neurobiol 2007; 33: 395- 7
  35. Liberski PP, Sikorska B, Hauw J-J, Kopp N, Streihenberger N, Giraud P, Budka H, Bollaard JW, Brown P. Tubulove- sicular structures are a consistent (and unexplained) finding in the brains of human prion diseases. Virus Res 2008; 136: 226-8
  36. Liberski PP, Streichenberger N, Giraud P, Soutrenont M, Meyeronnett M, Sikorska B, Kopp N. Ultrastructural pathology of prion diseases revisited: brain biopsy studies. Neuropathol Appl Neurobiol 2005; 31: 88-96 41
  37. Merz P, Wisniewski HM, Somerville RA, Bobin SA, Masters CL, Iqbal K. Ultrastructural morphology of amyloid fibrils from neuritic and amyloid plaques. Acta Neuropathol (Berl) 1983; 60: 113-24 42
  38. Masliah E, Mallory M, Deerinck T, DeTeresa R, Lamont S, Miller A, Terry RD, Carragher B, Ellisman M. Re-evaluation of the structural organization of neuritic plaques in Alzheimer's disease. J Neuropathol Exp Neurol 1993; 52: 619-32
  39. Liberski PP, Kloszewska I, Boellaard I, Papierz W, Omulecka A, Budka H. Dystrophic neurites of Alzhe- imer's disease and Gerstmann-Sträussler-Scheinker's disease dissociate from the formation of paired helical filaments. Alzheimers Res 1995; 1: 89-93 44
  40. Ishizawa K, Komori T, Shimazu T, Yamamoto T, Kita- moto T, Shimazu K, Hirose T. Hyperphosphorylated tau deposition parallels prion protein burden in a case of Gerstmann Sträussler Scheinker syndrome P102L muta- tion complicated with dementia. Acta Neuropathol 2002; 104: 342-50
  41. Liberski PP, Budka H. Neuroaxonal pathology in Creutzfeldt Jakob disease. Acta Neuropathol 1999; 97: 329-34
  42. Cervenakova L, Goldafrb LG, Garruto R, Lee HS, Gajdusek DC, Brown P. Phenotype -genotype studies in kuru: Implications for new variant Creutfeldt Jakob disease. Proc Natl Acad Sci 1998; 96: 13239-41 48
  43. McLean CA, Ironside JW, Alpers MP, Brown P, Cervena- kova L, Anderson RMcD, Masters CL. Comparative neuropathology of kuru with the new variant of Creutzfeldt Jakob disease: evidnence for strain of agent predominating over genotype of host. Brain Pathol 1998; 8: 429-37 49
  44. Hill AF, Desbruslais M, Joiner S, Sidle KCL, Gowland I, Collinge J, Doey LJ, Lantos P. The same prion strain causes vCJD and BSE. Nature 1997; 389: 448-50 50
  45. Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardle L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock C. Transmission of mice indicate that 'new variant' CJD is caused by the BSE agent. Nature 1997; 389: 498-501
  46. Scott MR, Will R, Ironside J, Nguyen HO, Tremblay P, DeArmond SJ, Prusiner SB. Compelling transgenic evi- dence for transmission of bovine spongiform encephal- opathy prions to humans. Proc Natl Acad Sci USA 1999; 96: 15137-42
  47. Fraser H. Neuropathology of scrapie: the precision of the lesions and their significance. In Slow Transmissible Diseases of the Nervous System Vol. 1. Eds SB Prusiner, WJ Hadlow. New York: Academic Press, 1979; 387- 406
  48. Jeffrey M, Goodsir CM, Bruce ME, McBride PA, Farquhar C. Morphogenesis of amyloid plaques in 87V murine scrapie. Neuropathol Appl Neurobiol 1994; 20: 535-42

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Authors
Sikorska, B., Liberski, P. P., Sobów, T., Budka, H., & Ironside, J. W.
Affiliations
  • Medical University of Lodz (PL)
  • Medical University of Vienna (AT)
  • University of Edinburgh (GB)
Corresponding author
Ironside, J. W.
ORCID
Venue
Neuropathology and Applied Neurobiology
Publisher
Wiley
Published
2009-01-21
Volume
35
Issue
1
Pages
46-59
ISSN
  • 0305-1846 (ISSN-L)
  • 1365-2990
DOI
10.1111/j.1365-2990.2008.00959.x
OpenAlex
W1979044678
Cited by
72
References
1
Citations by year
2025: 2 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 7 · 2016: 5 · 2015: 4 · 2013: 7 · 2012: 8
FWCI
2.06
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Neuropathology and Applied Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Funders
Uniwersytet Łódzki
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
Keywords
variant Creutzfeldt-Jakob disease, amyloid plaques, ultrastructure, kuru, sporadic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, Alzheimer's disease, dystrophic neurites, microglia, prion disease
MeSH terms
Adolescent, Adult, Alzheimer Disease, Amyloid, Brain, Brain Chemistry, Female, Glial Fibrillary Acidic Protein, Gliosis, Humans, Creutzfeldt-Jakob Syndrome, Kuru, Male, Neurons, Endosomes, Gerstmann-Straussler-Scheinker Disease, tau Proteins, Microglia, Ubiquitin, Plaque, Amyloid

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