Positive transmission of Creutzfeldt-Jakob disease verified by murine kuru plaques.

Kuru plaque is a pathognomonic feature in the brain of patients with Creutzfeldt-Jakob disease (CJD) and in the brain of CJD-infected mice. Kuru plaques from CJD-infected mice were immunolabeled with rabbit anti-murine prion protein (PrP) absorbed with human PrP, but not so with mouse anti-human PrP. Therefore, the murine kuru plaque is composed of the host (mouse) PrP and can be distinguished antigenically from human PrP. Immunostaining using the anti-murine PrP and formic acid enhancement on tissue sections revealed not only birefringent kuru plaques but also nonbirefringent diffuse and small PrP accumulations. This immunohistochemical detection of kuru plaques provides more positive evidence than heretofore employed histochemical approaches. There were kuru plaques in brains of the first passage mice inoculated with tissues from 30 (91%) of 33 patients with CJD, the 3 negative patients belonging to a type of Gerstmann-Sträussler syndrome. Tissues from 6 other demented patients did not produce kuru plaques. In the evaluation of spongiform changes, mice inoculated with tissues from 23 (70%) of 33 patients were considered cases of successful transmission. In some mice, kuru plaques were present in the absence of spongiform changes. Further inoculations from 9 mice with kuru plaques but no spongiform changes were successful in almost all mice. Therefore, mice with murine kuru plaques in the absence of spongiform changes are also infectious. Thus, the presence of murine-specific kuru plaques can serve as another hallmark of a successful transmission.