Wide distribution of prion infectivity in the peripheral tissues of vCJD and sCJD patients

Jean-Yves Douet,Didier Vilette,Hervé Cassard,Naima Aron,Mark Arnold,Alvina Huor,Juan-Maria Torres,James W Ironside,Séverine Lugan,Olivier Andreoletti

doi:10.1007/s00401-021-02270-x

Abstract

Sporadic Creutzfeldt-Jakob disease (sCJD) is the commonest human prion disease, occurring most likely as the consequence of spontaneous formation of abnormal prion protein in the central nervous system (CNS). Variant Creutzfeldt–Jakob disease (vCJD) is an acquired prion disease that was first identified in 1996. In marked contrast to vCJD, previous investigations in sCJD revealed either inconsistent levels or an absence of PrPSc in peripheral tissues. These findings contributed to the consensus that risks of transmitting sCJD as a consequence of non-CNS invasive clinical procedures were low. In this study, we systematically measured prion infectivity levels in CNS and peripheral tissues collected from vCJD and sCJD patients. Unexpectedly, prion infectivity was detected in a wide variety of peripheral tissues in sCJD cases. Although the sCJD infectivity levels varied unpredictably in the tissues sampled and between patients, these findings could impact on our perception of the possible transmission risks associated with sCJD.

Highlights

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders that affect a large spectrum of mammalian species
Each sample (10% tissue homogenates) was inoculated by the intracerebral route (IC) to bovine PrP expressing mice; a bioassay model identified in previous studies as a sensitive and robust approach for the detection and the quantification of Variant Creutzfeldt–Jakob disease (vCJD) infectivity [15, 17]
Each of the 14 different categories of peripheral tissues caused, at variable extent, occurrence of clinical TSE in Transgenic mice expressing bovine PrP (tgBov). Based on these transmission results, the pattern of vCJD infectivity in peripheral tissues was relatively similar across the four vCJD patients (Table 2)

Summary

Introduction

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are fatal neurodegenerative disorders that affect a large spectrum of mammalian species. Whereas familial disease forms are linked to pathogenic mutations in the human prion protein gene (PRNP), no clear epidemiologic risk factors have been identified for sporadic disease forms [57]. In the absence of identifiable external sources that might explain sCJD occurrence, it is currently assumed that this disease is triggered by the spontaneous and stochastic formation of a misfolded PrP nucleus in the brain of the affected individual. This original nucleus is considered to recruit and convert fresh PrPC into PrPSc leading to the progressive spread and propagation of prions in the brain of the diseased patient. In fCJD cases, PRNP mutations foster the formation of the initial misfolded PrP nucleus, leading to an increased probability of development of the disease [14]

Methods

Results

Conclusion