Transmissibility of Atypical Scrapie in Ovine Transgenic Mice: Major Effects of Host Prion Protein Expression and Donor Prion Genotype

Atypical scrapie or Nor98 has been identified as a transmissible spongiform encephalopathy (TSE) that is clearly distinguishable from classical scrapie and BSE, notably regarding the biochemical features of the protease-resistant prion protein PrPres and the genetic factors involved in susceptibility to the disease. In this study we transmitted the disease from a series of 12 French atypical scrapie isolates in a transgenic mouse model (TgOvPrP4) overexpressing in the brain ∼0.25, 1.5 or 6× the levels of the PrPARQ ovine prion protein under the control of the neuron-specific enolase promoter. We used an approach based on serum PrPc measurements that appeared to reflect the different PrPc expression levels in the central nervous system. We found that transmission of atypical scrapie, much more than in classical scrapie or BSE, was strongly influenced by the PrPc expression levels of TgOvPrP4 inoculated mice. Whereas TgOvPrP4 mice overexpressing ∼6× the normal PrPc level died after a survival periods of 400 days, those with ∼1.5× the normal PrPc level died at around 700 days. The transmission of atypical scrapie in TgOvPrP4 mouse line was also strongly influenced by the prnp genotypes of the animal source of atypical scrapie. Isolates carrying the AF141RQ or AHQ alleles, associated with increased disease susceptibility in the natural host, showed a higher transmissibility in TgOvPrP4 mice. The biochemical analysis of PrPres in TgOvPrP4 mouse brains showed a fully conserved pattern, compared to that in the natural host, with three distinct PrPres products. Our results throw light on the transmission features of atypical scrapie and suggest that the risk of transmission is intrinsically lower than that of classical scrapie or BSE, especially in relation to the expression level of the prion protein

Representation of Vulnerability and the Elderly : A Total Survey Error Perspective on the VLV Survey

This chapter focuses on the "Vivre-Leben-Vivere" (VLV) research and explains how the team in charge has dealt with the issue of representing old people in Switzerland and the vulnerable persons within this population. For this purpose, we draw inspiration from the "total survey error" perspective and discuss the procedures that were used to collect the information, but also the quality of the information itself. We present some of VLV's methodological choices, such as the contact procedures that were designed to "capture" the most vulnerable individuals, especially in a context where refusal rates for participation in surveys are increasing. We also consider the missing values in responses to some "complex" topics. Results show that participation rates are highly related to the effort that was made in order to recruit the individuals. This is critical for the VLV project, where people can show different degrees of vulnerability related to age, health, and/or poverty. In this sense, efforts such as repeated calls, home visits, and the proxy procedure were successful both in a general perspective and more specifically for a fair inclusion of vulnerable persons in the survey. At the same time, the non-response rates show to what extent it is difficult to explain the personal decision not to respond to a survey or to a question. We can find some traces of "interviewer effects" in the analysis of item non-responses, which we have done by using a logistic regression for one of the psychological tests included in VLV. Some aspects relate to interviewer and respondent characteristics, but others relate to the interview context, all highlighting the complex social interactions at stake