Nature Medicine  11, 982 - 985 (2005)
Published online: 28 August 2005; | doi:10.1038/nm1286

Detection of prions in blood

Joaquín Castilla¹, Paula Saá^1, 2 & Claudio Soto¹

¹  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 (PrP^Sc)¹. The development of highly sensitive assays for biochemical detection of PrP^Sc 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 PrP^Sc. 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 PrP^Sc. Notably, serial PMCA enables detection of PrP^Sc in blood samples of scrapie-afflicted hamsters with 89% sensitivity and 100% specificity. These findings represent the first time that PrP^Sc has been detected biochemically in blood, offering promise for developing a noninvasive method for early diagnosis of prion diseases.