Detection of prions in blood

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 disease(2). Here we show that the protein misfolding cyclic amplification ( PMCA) technology(3) 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.