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The cause of the original case or cases of bovine spongiform encephalopathy (BSE) remains an enigma. Sheep scrapie or a previously undetected sporadic bovine transmissible spongiform encephalopathy (TSE) have long been considered as candidates, but no convincing evidence to support these proposals has come to light. We present a new theory, with three related hypotheses: (1) that BSE was acquired from a human TSE (prion disease); (2) that the route of infection was oral, through animal feed containing imported mammalian raw materials contaminated with human remains; and (3) that the origin was the Indian subcontinent, from which large amounts of mammalian material were imported during the relevant time period. Human remains are known to be incorporated into meal made locally, and may still be entering exported material. Further investigations are needed into the sources of animal by-products used in animal feed manufacture, and into the the transmissibility of human TSEs to cattle.

Context: National prospective collection of tonsillar tissue to be tested anonymously for abnormal lymphoreticular accumulation of prion protein (PrP) was approved to begin in the UK in 2004. The UK is not, however, testing autopsy specimens attributably for abnormal PrP (PrP(SC)) so that recipients at risk after a blood transfusion from, or exposed to surgical instruments from, a deceased carrier of variant Creutzfeldt-Jakob disease (vCJD) can be followed up to quantify transmission risks. In Switzerland, surveillance for subclinical vCJD includes unconsented testing in autopsies: consented testing of tonsillar tissue is potentially attributable to interrupt human-to-human vCJD transmission or treat it., Starting Point: The UK announced its first case of probable blood-borne vCJD transmission in December, 2003, and first detected a case of probable blood-borne subclinical vCJD in July, 2004. To reduce the possible risk of onward transmission to other people, UK patients who had received vCJD-implicated plasma products are being contacted. They, and their general practitioner, are asked to inform anyone giving them medical, surgical, or dental treatment, and the patients must refrain from donating blood, tissues, or organs. WHERE NEXT? Prudent additional surveillance options for human PrP(SC)--particularly at autopsy or to sanction the release of quarantined operation sets pending effective decontamination--can be costed by reference to results for cattle and sheep. Some ethical or legal impediments to the UK's potentially-attributable testing for PrP(SC) may yet be rued.

The term "prion dementia" has been proposed to replace "spongiform encephalopathy", to accommodate the existence of atypical forms of these "prion protein" (PrP) cerebral amyloidoses that may not show spongiform changes in the brain. We tested brain tissue extracts for the presence of PrP from 46 cases (including 13 familial cases) of non-spongiform dementias with a variety of associated neurological signs, referred to our laboratory for primate transmission studies. None of the cases transmitted disease to primates, and none had PrP detectable by western immunoblots of extracted brain tissue. We conclude that prion dementias are not lurking undetected within the larger landscape of neurodegenerative disorders, and that their clinicopathological limits are, except for a small number of previously reported familial cases, essentially those of spongiform encephalopathy.

The polymerase chain reaction was used to screen DNA samples from 12 unrelated individuals with various familial dementias and ataxias for mutation in part of the prion protein (PrP) gene, an abnormality that occurs in individuals with the spongiform encephalopathies, Gerstmann-Sträussler syndrome (GSS) and Creutzfeldt-Jakob disease. 2 members of a family in whom GSS was not previously suspected had a 0.15 kb insertion of similar size to that found in another kindred with pathologically proven spongiform encephalopathy. GSS may be more common than is currently realised; PrP gene analysis is potentially useful for diagnosis and genetic counselling in familial dementias and ataxias.