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Detection of prions in blood

Nature Medicine volume 11, pages 982–985 (2005)Cite this article

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Abstract

Prion diseases are caused by an unconventional infectious agent termed prion, composed mainly of the misfolded prion protein (PrPSc)1. The development of highly sensitive assays for biochemical detection of PrPSc in blood is a top priority for minimizing the spread of the disease2. Here we show that the protein misfolding cyclic amplification (PMCA) technology3 can be automated and optimized for high-efficiency amplification of PrPSc. We show that 140 PMCA cycles leads to a 6,600-fold increase in sensitivity over standard detection methods. Two successive rounds of PMCA cycles resulted in a 10 million–fold increase in sensitivity and a capability to detect as little as 8,000 equivalent molecules of PrPSc. Notably, serial PMCA enables detection of PrPSc in blood samples of scrapie-afflicted hamsters with 89% sensitivity and 100% specificity. These findings represent the first time that PrPSc has been detected biochemically in blood, offering promise for developing a noninvasive method for early diagnosis of prion diseases.

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Figure 1: Automated PMCA enables ultrasensitive detection of minute quantities of PrPSc.
Figure 2: PrPSc detection in blood of scrapie infected hamsters by saPMCA.
Figure 3: Comparison of the quantity of PrPSc in brain and blood.

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Change history

  • 11 January 2013

     In the version of this article initially published, there was a mistake in Figure 2. Several bands depicted in the second round of protein misfolding cyclic amplification were inadvertently duplicated in the third round. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We would like to thank K. Maundrell (Serono Pharmaceutical Research Institute, Geneva, Switzerland) for bringing to our attention the automatic sonicator. C.S. is part of the European Community project TSELAB. This research was supported in part by US National Institutes of Health grants AG0224642 and NS049173 and the Intramural John Sealy Endowed Fund for Biomedical Research.

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Authors and Affiliations

  1. Departments of Neurology, Human Biological Chemistry & Genetics and Neuroscience & Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, 77555-0646, Texas, USA

    Joaquín Castilla, Paula Saá & Claudio Soto

  2. Centro de Biología Molecular, Universidad Autónoma de Madrid, Madrid, 28409, Spain

    Paula Saá

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  1. Joaquín Castilla
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Correspondence to Claudio Soto.

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Castilla, J., Saá, P. & Soto, C. Detection of prions in blood. Nat Med 11, 982–985 (2005). https://doi.org/10.1038/nm1286

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