Study Links Rise in Sporadic CJD to BSE

The eating of BSE-infected meat might cause classical CJD in people, as well as variant CJD, a new study using mice suggests. Classical CJD, also called sporadic CJD (sCJD), is generally believed to develop spontaneously and existed before the BSE epidemic in British cattle, while variant CJD (vCJD) is thought to be the human form of mad cow disease. There has been a recent rise in cases of sCJD, in the UK in particular, but it had been thought this was due to better surveillance and diagnosis. The surprising new finding appears to add weight to suggestions that the rise is in fact linked to the BSE epidemic.

The new work involved injecting the BSE infectious agent - a misfolded prion protein - into the brains of mice. The mice had been genetically modified to act as human models of infection and to be susceptible to CJD.

As expected, some of these mice developed symptoms and a molecular subtype of prion protein misfolding associated with vCJD. But others developed a sub-type associated with the most common of three strains of sCJD previously identified in people. "This finding has important potential implications," the team led by John Collinge at the MRC Prion Unit in London, UK, writes in the EMBO Journal. "It raises the possibility that some humans infected with BSE prions may develop a clinical disease indistinguishable from classical CJD."Models predicting the future extent of the human epidemic associated with eating BSE-infected meat are based on the observation of vCJD in the population. But if BSE prions can also cause sCJD, these models will underestimate the ultimate human death toll. To date, 117 people have died in the UK from vCJD.
Source: New Scientist
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Variant Creutzfeldt–Jakob disease (vCJD) has been recognized to date only in individuals homozygous for methionine at PRNP codon 129. Here we show that transgenic mice expressing human PrP methionine 129, inoculated with either bovine spongiform encephalopathy (BSE) or variant CJD prions, may develop the neuropathological and molecular phenotype of vCJD, consistent with these diseases being caused by the same prion strain. Surprisingly, however, BSE transmission to these transgenic mice, in addition to producing a vCJD-like phenotype, can also result in a distinct molecular phenotype that is indistinguishable from that of sporadic CJD with PrPSc type 2. These data suggest that more than one BSE-derived prion strain might infect humans; it is therefore possible that some patients with a phenotype consistent with sporadic CJD may have a disease arising from BSE exposure.
Source: European Molecular Biology Journal
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