New form of BSE resembles sporadic CJD

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Feb 19, 2004 (CIDRAP News) – Italian researchers this week reported a new form of bovine spongiform encephalopathy (BSE), or mad cow disease, that resembles sporadic Creutzfeldt-Jakob disease (CJD), a human brain disease that has not previously been linked to BSE.

Eating meat products from cows infected with BSE is believed to be the cause of variant Creutzfeldt-Jakob disease (vCJD), which has killed about 150 people, nearly all of them in the United Kingdom, since 1990. Sporadic CJD, so called because its cause is unknown, afflicts about 1 in 1 million people in the United States annually.

The Italian researchers found the new form of BSE in two of eight BSE-infected cows they analyzed, according to the online report in the Proceedings of the National Academy of Sciences. The two cows had a different pattern of brain damage and a different form of misfolded prion protein than what is normally seen in BSE. The cow brains had the spongy holes typically seen in BSE but also featured amyloid plaques, or waxy clumps, not previously described in BSE-infected cows.

Both the pattern of brain damage and the strain of misfolded prion resembled what is seen in one subtype of sporadic CJD, according to the report. The findings suggest the possibility that some cases of sporadic CJD may actually come from eating beef. But the Italian researchers caution against jumping to conclusions and say further research is needed to better characterize the prion proteins associated with the new type of BSE and sporadic CJD.

The Italian report was edited by Stanley Prusiner, a pioneering prion-disease researcher. The eight BSE-infected cows were among 103 cases found since 2001 in Italy, where more than 1.6 million cattle have been tested for the disease in that time. In examining the cows' brains, the researchers found that two of the cattle, which were older than the others at 15 and 11 years, had "striking differences in the patterns and topography" of prion protein deposition, the report says.

The six younger cows had granular and thread-like deposits of prion protein, mainly in the brain stem and thalamus—typical findings in BSE. In contrast, the two older cows had amyloid plaques of prion protein concentrated in the thalamus, cerebral cortex, and olfactory bulb, with little deposition in the brain stem. BSE typically involves prion deposits in the dorsal nucleus of the vagus nerve, but these were absent in the two older cows.

The researchers also found differences in the "molecular signatures" of the prion protein from the two groups of cows. Brain tissue from the cows was compared with samples from sporadic CJD–infected brains featuring different subtypes of prion protein. "Strikingly, the molecular signature of this previously undescribed bovine PrPSc [pathogloic prion protein] was similar to that encountered in a distinct subtype of sporadic Creutzfeldt-Jakob disease," called sporadic CJD methionine/valine 2 (sCJD M/V 2), the authors write.

Because of the distinct brain pathology and prion-protein properties in the two older cows, the researchers propose to name the disease "bovine amyloidotic spongiform encephalopathy," or BASE. They write that the absence of disease in the vagus nerve and slight involvement of the brainstem suggests that the cows contracted the disease by some route other than feeding. "It is possible that this disorder represents a sporadic form of cattle TSE, which would also explain the difference in ages between the two groups of infected animals," the report states.

The researchers note that while the brain pathology and the type of prion protein in the older cows resembled those seen in sporadic CJD M/V 2, there were some differences in the distribution of the prion protein in the brain. "Although BASE and sCJD share several characteristics, caution is dictated in assessing a link between conditions affecting two different mammalian species, based on convergent biochemical properties of disease-associated PrPSc types," the article states.

The authors add that they hope to gather more information about strains of transmissible spongiform encephalopathy (TSE) agents through research in genetically modified mice. "Until this is accomplished, our present findings suggest a strict epidemiological surveillance of cattle TSE and sCJD based on molecular criteria," they conclude.

Shaun Kennedy, associate director of the University of Minnesota Center for Animal Health and Food Safety, commented, "If this study is proven correct, it would suggest there is a sporadic form of cattle TSE, or less likely, that there's another way for propagation of BSE other than the alimentary tract, which would be unusual." If a sporadic form of cattle TSE exists, it could be what started the BSE outbreaks in Britain in the 1980s, he suggested.

Concerning the possibility that sporadic CJD could be related to eating beef, Kennedy said, "It's already been demonstrated that humans can get [vCJD] from eating infected meat, so that's not new." He said the existence of BASE wouldn't change the US Department of Agriculture's approach to testing cattle for BSE or other BSE safeguards. The disease was found in older cattle, and the USDA testing program focuses on older animals as well as those with signs of disease, he said. "You'd find this kind [of BSE] just like you'd find the others," he added.

Pam Skinner, a microbiologist in the University of Minnesota Department of Veterinary and Biomedical Sciences, said the report prompts her to wonder about the transmissibility of BASE. BSE doesn't spread directly from animal to animal, but chronic wasting disease, a TSE found in deer and elk, does spread that way, she noted. "We don't know about this new strain of BSE, what it takes to transmit from one animal to another,"she said. "If it's more easily transmitted, that would have serious implications." Another question, she added, is whether the disease can cross into different species.

Casalone C, Zanusso G, Acutis P, et al. Identification of a second bovine amyloidotic spongiform encephalopathy: molecular similarities with sporadic Creutzfeldt-Jakob disease. Proc Nat Acad Sci 2004;101(9):3065-70 [ Abstract]

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