Nature Medicine
11, 982 - 985 (2005)
Published online: 28 August 2005; | doi:10.1038/nm1286
Detection of prions in bloodJoaquín Castilla1, Paula Saá1, 2
& Claudio Soto11
Departments of Neurology, Human Biological Chemistry & Genetics and Neuroscience & Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas, 77555-0646, USA. 2
Centro de Biología Molecular, Universidad Autónoma de Madrid, Madrid 28409, Spain.
Correspondence should be addressed to Claudio Soto clsoto@utmb.edu 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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