Since the first cases of BSE appeared in the UK in 1986, the question as to the origin of BSE has posed a major challenge to the scientific community. Recently published data indicates that the occurrence of a spontaneous prion disease in cattle may have been the original cause of the BSE epidemic.

While Creutzfeldt-Jakob disease (CJD) and sheep scrapie are known to appear as many different strains, the BSE epidemic in the UK appears to have been caused by a single strain of BSE resulting in a unique lesion profile in the brains of infected animals. Today, scientists are studying whether or not BSE occurs as a sporadic disease, and was simply not recognized as such due to lack of awareness, or did it come about by transmission of other TSE agents - such as scrapie. In the last two years new, atypical cases of BSE have been detected in Italy, France and Japan, suggesting the existence of more than one strain of BSE. This finding has supported the notion that the BSE epidemic might have had its origin in a sporadic form of BSE occurring with very low frequency in cattle.
The Italian atypical BSE cases were unusual inasmuch as they presented with PrP deposition in amyloid plaques, a feature which has not been associated with typical BSE. These findings prompted Italian scientists to name this disease BASE, for Bovine Amyloidotic Spongiform Encephalopathy. In addition, the biochemical fingerprint of PrPSc associated with BASE was found to be distinct from BSE.

BASE converts to BSE
This same group of Italian scientists also showed that BASE is transmittable from cattle to mice. The scientists used transgenic mice expressing bovine PrP and four lines of normal inbred mice, expressing mouse PrP, in their transmission studies. The BASE isolates were efficiently transmitted to the transgenic mice expressing bovine PrP. Importantly, the strain specific features of BASE, such as brain lesion profile and biochemical fingerprint of PrP, were maintained upon passage in the transgenic host. In contrast, no clinical symptoms were developed upon first passage in inbred mice. Surprisingly, upon second passage of BASE prions in these mice, the animals developed a disease strikingly similar to BSE. The scientists concluded that the BASE strain is converted into the BSE strain upon serial passage in the new host. This important finding suggests that BASE might represent the original strain of BSE which was modified in cattle to obtain properties that facilitated transmission to other species including humans.

BASE linked to sCJD?
Since the biochemical profile and the form of PrP depositions in the brain associated with BASE are very similar to those found in some types of sporadic CJD (sCJD), the question now is whether or not a similar link between BASE and sCJD cases exist as between classical BSE and variant CJD. Although it may be too early for such far-reaching conclusions based on a molecular characterization of a small number of novel BSE phenotypes, there is certainly enough justification to continue monitoring the occurrence of atypical BSE cases by active surveillance.