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In vitro amplification and detection of variant Creutzfeldt-Jakob disease PrPSc

Jones, M.ORCID: 0000-0001-5002-0227, Peden, A.H., Prowse, C.V., Gröner, A., Manson, J.C., Turner, M.L., Ironside, J.W., MacGregor, I.R. and Head, M.W. (2007) In vitro amplification and detection of variant Creutzfeldt-Jakob disease PrPSc. The Journal of Pathology, 213 (1). pp. 21-26.

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Variant Creutzfeldt–Jakob disease (vCJD) poses a serious risk of secondary transmission and the need to detect infectivity in asymptomatic individuals is therefore of major importance. Following infection, it is assumed that minute amounts of disease‐associated prion protein (PrPSc) replicate by conversion of the host cellular prion protein (PrPC). Therefore, methods of rapidly reproducing this conversion process in vitro would be valuable tools in the development of such tests. We show that one such technique, protein misfolding cyclic amplification (PMCA), can amplify vCJD PrPSc from human brain tissue, and that the degree of amplification is dependent upon the substrate PRNP codon 129 polymorphism. Both human platelets and transgenic mouse brain are shown to be suitable alternative substrate sources, and amplified PrPSc can be detected using a conformation‐dependent immunoassay (CDI), allowing the detection of putative proteinase K sensitive forms of PrPSc.

Item Type: Journal Article
Publisher: John Wiley & Sons, Ltd.
Copyright: Copyright © 2007 Pathological Society of Great Britain and Ireland.
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