For the first time, researchers have developed an in vitro technique to detect the presence of prions in blood samples. An effective blood test for these lethal brain diseases could allow for early diagnosis as well as for curbing their transmission.

Prion diseases—including variant Creutzfeldt-Jakob disease (vCJD), the human form of mad cow disease—arise through an accumulation of misfolded, self-replicating proteins in the brain that results in neurodegeneration and death. These diseases can incubate for decades before symptoms appear.

Since the first wave of vCJD occurred in the United Kingdom in the late 1990s, the medical community has been looking for a quick and reliable test for diagnosis of prion diseases. However, the prion proteins, which concentrate in the brain, are present in undetectable levels in the blood. No one has yet developed a biochemical test; definitive diagnosis of vCJD occurs only at autopsy.

Now, Claudio Soto of the University of Texas Medical Branch (Galveston, TX) and his colleagues have devised a way to amplify and detect the presence of prions in blood samples (Nat. Med., September). Upon incubation of a minute amount of the prion protein PrPSc with an excess of the normal protein PrPC, the prion protein changes the conformation of the surrounding normal proteins, causing the formation of protein aggregates in the sample. Sonication causes the aggregates to break up, releasing more PrPSc, which form the basis of new PrPSc clusters.

Soto's group tested the effectiveness of the assay using blood samples taken from hamsters showing symptoms of the prion disease scrapie. They ran 140 cycles and, using western blot, detected the prion protein 89% of the time, with no false positives.

Soto's group is now using this amplification method to determine the earliest point during the incubation period at which prion proteins can be detected in the blood. In addition, they are adapting the technique to detect prions in humans and cattle.

A reliable blood test for prion detection would have several important uses, including prevention of accidental transmission through blood transfusion and organ transplant and large-scale screening to prevent the entry of diseased animals into the food supply.