It is widely accepted that abnormal forms of the
prion protein (PrP) are the best
surrogate marker for the infectious agent of
prion diseases and, in practice, the detection of such disease-associated (
PrP(d)) and/or
protease-resistant (
PrP(res)) forms of PrP is the cornerstone of diagnosis and surveillance of the
transmissible spongiform encephalopathies (TSEs). Nevertheless, some studies question the consistent association between infectivity and abnormal PrP detection. To address this discrepancy, 11 brain samples of sheep affected with natural
scrapie or experimental
bovine spongiform encephalopathy were selected on the basis of the magnitude and predominant types of
PrP(d) accumulation, as shown by immunohistochemical (IHC) examination; contra-lateral hemi-brain samples were inoculated at three different dilutions into transgenic mice overexpressing ovine PrP and were also subjected to quantitative analysis by three biochemical tests (BCTs). Six samples gave 'low' infectious titres (10⁶·⁵ to 10⁶·⁷ LD₅₀ g⁻¹) and five gave 'high titres' (10⁸·¹ to ≥ 10⁸·⁷ LD₅₀ g⁻¹) and, with the exception of the Western blot analysis, those two groups tended to correspond with samples with lower
PrP(d)/
PrP(res) results by IHC/BCTs. However, no statistical association could be confirmed due to high individual sample variability. It is concluded that although detection of abnormal forms of PrP by laboratory methods remains useful to confirm TSE
infection, infectivity titres cannot be predicted from quantitative test results, at least for the TSE sources and host PRNP genotypes used in this study. Furthermore, the near inverse correlation between infectious titres and Western blot results (high
protease pre-treatment) argues for a dissociation between infectivity and
PrP(res).