The Generative Brain

Casalone C et al. 2004, Identification of a second bovine amyloidotic spongiform encephalopathy, molecular similarities with sporadic Creutzfeldt-Jakob disease (PNAS 101:3065-3070, PMID 14970340)

A 2004 PNAS paper from the Italian national reference centre for animal encephalopathies in Turin, with neurologists in Verona, the Brescia veterinary institute and the Carlo Besta institute in Milan, that described a second form of prion disease in cattle. Unlike typical BSE, the two affected animals had prion protein amyloid plaques, a different brain distribution of abnormal prion protein and a lighter protease-resistant fragment dominated by the single sugar chain form. The authors named it bovine amyloidotic spongiform encephalopathy (BASE), now usually called L-type atypical BSE, and pointed out that its molecular signature looked like a subtype of sporadic CJD. Together with the French EMBO Reports paper of the same period, it began the study of atypical BSE. It concerns cattle, not human patients, and it did not show that BASE causes any human disease. Information only, not medical or veterinary advice.

Key facts

  • The eight authors came from four Italian centres: the Turin zooprophylactic institute reference centre (Casalone, Acutis, Caramelli), the Verona neurology department at Policlinico G.B. Rossi (Zanusso, Ferrari, and corresponding author Monaco), the Brescia zooprophylactic institute (Capucci) and the Carlo Besta neurological institute in Milan (Tagliavini); Casalone and Zanusso are listed as equal first authors.
  • The paper was received on 9 September 2003, edited by Stanley Prusiner, and published online on 17 February 2004 in volume 101, issue 9, pages 3065 to 3070.
  • According to the abstract, the new form showed PrP-positive amyloid plaques, which typical BSE lacks, a different regional pattern of abnormal prion protein, and a protease-resistant fragment of lower mass than in BSE with the low mass glycoform dominant.
  • The authors reported that this molecular signature resembled a distinct subtype of sporadic CJD; a contemporary news report and the earlier atlas reading both identify it as the MV2 subtype.
  • A 2004 news report on the paper says the team examined 8 of the 103 Italian BSE cases found since 2001 among more than 1.6 million cattle tested, and that the 2 atypical animals were aged 15 and 11 while the 6 typical cases were younger.
  • The same report says the atypical animals had plaques mainly in the thalamus, cerebral cortex and olfactory bulb with little brain stem involvement, and that the authors suggested a route other than feed because the vagus nerve was spared, while warning against reading a species link from protein similarity alone.
  • Follow-on Italian work showed that BASE behaved differently from BSE in mice and that serial passage in wild type mice gave a BSE-like disease (Carlo Besta, 2007), and that BASE transmitted to cattle by brain inoculation reproduced the original profile with mental dullness and muscle wasting (Brescia and Verona, 2008).
  • Transmission studies raised the human question: BASE material infected about 60 percent of human PrP mice after 20 to 22 months (Case Western, January 2008), L-type isolates spread in human PrP mice with no obvious barrier (INRA Jouy-en-Josas, December 2008), and one macaque given BASE had a shorter survival than BSE inoculated animals (CEA, August 2008).
  • Later work in the atlas tempers this: L-type BSE gave disease in macaques in about 2 years at the lowest doses tested, while a 2016 Jouy study found no evidence that L-type BSE causes a known form of sporadic CJD in human PrP mice.
  • Europe PMC counted 293 citing papers on 21 October 2026.

Timeline

  1. 2003Manuscript received by PNAS (9 September).
  2. 2004Published online on 17 February 2004; CIDRAP reports it on 19 February.
  3. 2004Print issue of 2 March 2004, PNAS 101(9):3065-3070.
  4. 2007Carlo Besta group reports conversion of BASE into a BSE-like strain in mice.
  5. 2008Case Western group reports BASE transmission to human PrP transgenic mice.
  6. 2008Brescia and Verona report intraspecies transmission of BASE in cattle.
  7. 2008CEA reports BASE transmission to a macaque.
  8. 2008INRA Jouy-en-Josas reports L-type transmission to human PrP mice without an obvious barrier.
  9. 2016Jouy-en-Josas paper finds no evidence that L-type BSE causes a known sporadic CJD form in human PrP mice.
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