Similarities between Forms of Sheep Scrapie and Creutzfeldt-Jakob Disease Are Encoded by Distinct Prion Types

Abstract

Transmissible spongiform encephalopathies such as scrapie in sheep, Creutzfeldt-Jakob disease (CJD) in humans, and bovine sporadic encephalopathy in cattle are characterized by the accumulation of a misfolded protein: the pathological prion protein. Ever since bovine sporadic encephalopathy was discovered as the likely cause of the new variant of CJD in humans , parallels between human and animal transmissible spongiform encephalopathies must be viewed under the aspect of a disease risk for humans. In our study we have compared prion characteristics of different forms of sheep scrapie with those of different phenotypes of sporadic CJD. The disease characteristics of sporadic CJD depend considerably on the prion type 1 or 2. Our results show that there are obvious parallels between sporadic CJD type 1 and the so-called atypical/Nor98 scrapie. These parelleles apply to the deposition form of pathological prion protein in the brain, detected by the paraffin-embedded-tissue blot and the prion aggregate stability with regard to denaturation by the chaotropic salt guanidine hydrochloride. The same applies to sporadic CJD type 2 and classical scrapie. The observed parallels between types of sporadic CJD and types of sheep scrapie demonstrate that distinct groups of prion disease exist in different species. This should be taken into consideration when discussing interspecies transmission.

Distinct Stability States of Disease-Associated Human Prion Protein Identified by Conformation-Dependent Immunoassay

“…In their study, the difference in GdnHCl 1/2 values was ϳ0.6 M between the two forms of CJD (GdnHCl 1/2 in vCJD, 1.85 M; GdnHCl 1/2 in MM1 sCJD, 2.45 M), which resembles the values obtained using a greater number of vCJD and sCJD cases and the CDI in this study. CSA analysis of PrP res in sCJD of the MM genotype has shown that type 1 PrP res is more stable than type 2 (7), and this observation has been extended using a rapid dot blot variation of the CSA to encompass the MV and VV genotypes in sporadic CJD cases (53). Moreover, a recent conference abstract suggests that this higher structural stability of sCJD MM1 (compared to that of sCJD MM2) is conserved when these diseases are transmitted to bank voles (40).…”

Hereditary Human Prion Diseases: an Update

“…In octa-peptide repeat insertion patients, immunohistochemical detection of PrP Sc aggregates usually shows a patchy or tigroid pattern (d-h). Conventional anti-prion immunohistochemistry is depicted either in brown (a-c, g-i) or in red color (e, f) for visualization, performed according the protocol from [124,125]. In paraffin-embedded tissue (PET) blots (a, i; [126]), prion aggregates are stained dark brown.…”

“…Similarly, abnormal PrP deposits may be absent (e, thalamus) or only focally detectable in areas with spongiform alteration such as the subiculum or cerebellar molecular layer (f). a-d H&E staining; e, f anti-prion immunohistochemistry[124,125] …”

Molecular Pathogenesis of Prion Diseases

“…Wemheuer et al proposed a correlation between classical and atypical/Nor98 scrapie in sheep and sCJD, showing that the two scrapie types share a number of striking similarities with human PrP Sc types in sCJD (Wemheuer et al, 2009) (Fig. 4).…”