JOURNAL ARTICLE

Clinical, neuropathological and immunohistochemical features of sporadic and variant forms of Creutzfeldt-Jakob disease in the squirrel monkey (Saimiri sciureus)

Lawrence Williams, Paul Brown, James Ironside, Susan Gibson, Robert Will, Diane Ritchie, Thomas R Kreil, Christian Abee
Journal of General Virology 2007, 88: 688-95
17251588
The squirrel monkey (Saimiri sciureus) 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(-1) or 10(-3) 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(TSE)). 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(TSE) distribution in the brains of sCJD and vCJD animals, similar to those seen in humans except that amyloid plaques were not present. PrP(TSE) 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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