1887

Abstract

The squirrel monkey () has been shown to be nearly as susceptible as the chimpanzee to experimentally induced Creutzfeldt–Jakob disease (CJD), and has been used extensively in diagnostic and pathogenetic studies. However, no information is available concerning the clinicopathological characteristics of different strains of human transmissible spongiform encephalopathy (TSE) in this species, in particular, strains of sporadic and variant CJD (sCJD and vCJD, respectively). Brain homogenates from patients with sCJD or vCJD were inoculated intracerebrally at dilutions of 10 or 10 into the left frontal cortex of squirrel monkeys. Animals were kept under continuous clinical surveillance during the preclinical and clinical phases of disease, and regularly underwent standardized behavioural testing. Brains from three animals in the sCJD and vCJD groups were examined histopathologically and immunohistochemically for the presence of pathognomonic misfolded protein (PrP). Overall, incubation periods and durations of illness were slightly shorter in monkeys infected with sCJD than in those infected with vCJD, but the earliest signs of illness (ataxia and tremors) were the same in both groups. Clinical disease in the sCJD monkeys was somewhat more severe and of shorter duration. Post-mortem examinations revealed distinctive patterns of spongiform change and PrP distribution in the brains of sCJD and vCJD animals, similar to those seen in humans except that amyloid plaques were not present. PrP was uniformly absent from peripheral lymphoid tissues in both groups of animals. Human strains of sCJD and vCJD cause distinguishable clinicopathological features in the squirrel monkey that can provide a baseline for the evaluation of future therapeutic studies.

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2007-02-01
2024-03-29
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References

  1. Azzolin M., Furlati S., Pellegrini G., Trombetti C. 1998; The Observer 3.0: the first study of behavior of a couple mother-calf of Tursiops truncatus . In Measuring Behavior ′98: Second International Conference on Methods and Techniques in Behavioral Research Groningen, The Netherlands: 18–21 August 1998
    [Google Scholar]
  2. Baker H. F., Ridley R. M., Wells G. A., Ironside J. W. 1998; Prion protein immunohistochemical staining in the brains of monkeys with transmissible spongiform encephalopathy. Neuropathol Appl Neurobiol 24:476–486 [CrossRef]
    [Google Scholar]
  3. Brown P., Preece M., Brandel J.-P., Sato T., McShane L., Zerr I., Fletcher A., Will R. G., Pocchiari M. other authors 2000; Human spongiform encephalopathy: iatrogenic Creutzfeldt-Jakob disease at the millennium. Neurology 55:1075–1081 [CrossRef]
    [Google Scholar]
  4. Goldfarb L. G., Brown P. 1995; The transmissible spongiform encephalopathies. Annu Rev Med 46:57–65 [CrossRef]
    [Google Scholar]
  5. Head M. W., Bunn T. J., Bishop M. T., McLoughlin V., Lowrie S., McKimmie C. S., Williams M. C., McCardle L., MacKenzie J. other authors 2004; Prion protein heterogeneity in sporadic but not variant Creutzfeldt-Jakob disease: UK cases 1991-2002. Ann Neurol 55:851–859 [CrossRef]
    [Google Scholar]
  6. Ironside J. W., Head M. W., Bell J. E., McCardle L., Will R. G. 2000; Laboratory diagnosis of variant Creutzfeldt-Jakob disease. Histopathology 37:1–9 [CrossRef]
    [Google Scholar]
  7. Kovacs G. G., Trabattoni G., Hainfellner J. A., Ironside J. W., Knight R. S., Budka H. 2002; Mutations of the prion protein gene phenotypic spectrum. J Neurol 249:1567–1582 [CrossRef]
    [Google Scholar]
  8. Lasmézas C. I., Fournier J.-G., Nouvel V., Boe H., Marce D., Lamoury F., Kopp N., Hauw J. J., Ironside J. other authors 2001; Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-Jakob disease: implications for human health. Proc Natl Acad Sci U S A 98:4142–4147 [CrossRef]
    [Google Scholar]
  9. Masters C. L., Rohwer R. G., Franko M. C., Brown P., Gajdusek D. C. 1984; The sequential development of spongiform change and gliosis of scrapie in the golden Syrian hamster. J Neuropathol Exp Neurol 43:242–252 [CrossRef]
    [Google Scholar]
  10. Parchi P., Giese A., Capellari S., Brown P., Schulz-Schaeffer W., Windl O., Zerr I., Budka H., Kopp N. other authors 1999; Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 46:224–233 [CrossRef]
    [Google Scholar]
  11. Ritchie D. L., Head M. W., Ironside J. W. 2004; Advances in the detection of prion protein in peripheral tissues of variant Creutzfeldt-Jakob disease patients using paraffin-embedded tissue blotting. Neuropathol Appl Neurobiol 30:360–368 [CrossRef]
    [Google Scholar]
  12. Will R. G., Ironside J. W., Zeidler M., Cousens S. N., Estibeiro K., Alperovitch A., Poser S., Pocchiari M., Hofman A., Smith P. G. 1996; A new variant of Creutzfeldt-Jakob disease in the UK. Lancet 347:921–925 [CrossRef]
    [Google Scholar]
  13. Will R. G., Zeidler M., Stewart G. E., Macleod M. A., Ironside J. W., Cousens S. N., Mackenzie J., Estibeiro K., Green A. J., Knight R. S. 2000; Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neurol 47:575–582 [CrossRef]
    [Google Scholar]
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