1 Scientific RepoRts | 5:17742 | DOI: 10.1038/srep17742 www.nature.com/scientificreports preclinical detection of infectivity and disease-speciic PrP in blood throughout the incubation period of prion disease Elizabeth B. sawyer, Julie Ann edgeworth † , Claire thomas, John Collinge & Graham S. Jackson Variant Creutzfeldt-Jakob disease (vCJD) is a fatal neurodegenerative disorder characterised by accumulation of pathological isoforms of the prion protein, PrP. Although cases of clinical vCJD are rare, there is evidence there may be tens of thousands of infectious carriers in the United Kingdom alone. This raises concern about the potential for perpetuation of infection via medical procedures, in particular transfusion of contaminated blood products. Accurate biochemical detection of prion infection is crucial to mitigate risk and we have previously reported a blood assay for vCJD. This assay is sensitive for abnormal PrP conformers at the earliest stages of preclinical prion disease in mice and precedes the maximum infectious titre in blood. Not only does this support the possibility of screening asymptomatic individuals, it will also facilitate the elucidation of the complex relationship that exists between the ensemble of abnormal PrP conformers present in blood and the relationship to infectivity. Creutzfeldt-Jakob disease (CJD) is an incurable neurodegenerative disorder characterised by the accu- mulation of pathological isoforms of the prion protein, PrP 1,2 . CJD may arise sporadically or be acquired through exposure to prions via contaminated surgical instruments or infected tissue, including dietary exposure to bovine spongiform encephalopathy (BSE) agents resulting in variant CJD (vCJD) 3 . As a consequence of widespread exposure to BSE prions via the UK food chain, it is thought that as many as 1 in 2000 of the population may be carriers of abnormal PrP isoforms 4 . Signiicant questions remain over the link between observation of these protein deposits in lymphatic tissue and the likelihood of developing vCJD, given that the relationship between infection in the lymphoid system and the brain is not clear and that the incubation period of the disease can be decades 5,6 . he possibility that there are silent carriers of vCJD within the population is a cause for concern not only for the individuals afected but also because of the potential for perpetuation of vCJD infection via medical and dental treatments, particularly the transfusion of contaminated blood products. Several animal studies have demonstrated that prion transmission can occur by blood transfusion 7,8 and that this is an extremely eicient route of infection 9 . Experimental observations have been echoed by conirmed secondary vCJD infections in humans who received blood products from apparently healthy donors who later developed prion disease 10–12 . his strongly suggests the presence of vCJD infectivity in blood and therefore the need for precautionary measures to prevent further infections, ideally to include testing for prion infection as recommended by the recent UK House of Commons Science and Technology Select Committee enquiry into vCJD. MRc Prion Unit, Department of neurodegenerative Disease, UcL institute of neurology, Queen Square, London WC1N 3BG, UK. † Present address: Human Tissue Authority, 151 Buckingham Palace Road, London SW1W 9SZ. Correspondence and requests for materials should be addressed to G.S.J. (email: g.s.jackson@prion.ucl.ac.uk) Received: 18 June 2015 accepted: 06 November 2015 Published: 03 December 2015 OPEN