Neuropathological and molecular comparison between clinical and asymptomatic bovine spongiform encephalopathy cases

Abstract

Interest in the proper neuropathological and molecular characterization of bovine spongiform encephalopathy (BSE) has increased since asymptomatic and atypical cases were detected in the cattle population by active disease surveillance. In this respect we investigated a total of 95 confirmed BSE cases originating from different active and passive surveillance categories (clinical suspects, emergency-slaughter, fallen stock and routinely slaughter) in Switzerland for their neuropathological and molecular phenotype. We looked for measurable differences between these categories in lesion profile, severity of spongiform change, degree of astrocytosis as well as immunohistochemical and molecular patterns of the disease-associated isoform of the prion protein (PrPd) in the caudal brainstem. Our results indicate significantly higher intensities of spongiform change in clinically affected compared to asymptomatic BSE cases. Similar effects were in trend observed for the intensities of PrPd deposition and astrocytosis, whereas the frequencies of morphological PrPd types and the molecular patterns in Western immunoblot were not different. Importantly, none of the animals included in this study revealed features of atypical BSE. Taken together, this study suggests that both clinically affected as well as asymptomatic Swiss BSE cases in cattle share the neuropathological and molecular phenotype of classical BSE and that asymptomatic classical BSE cases are at a pre-clinical stage of the disease rather than representing a true sub-clinical form of BSE.

Relationship between clinical signs and postmortem test status in cattle experimentally infected with the bovine spongiform encephalopathy agent

“…The more frequent occurrence of locomotor and sensory signs in cattle with vacuolar changes compared to those with no or equivocal vacuolation (Table 2) suggests that vacuolation coincides with a more advanced clinical stage. This is in agreement with the findings in a Swiss study, where clinical suspect BSE cases had more severe spongiform changes in the brain than BSE cases slaughtered as apparently healthy cattle [33]. …”

A C-Terminal Protease-Resistant Prion Fragment Distinguishes Ovine “CH1641-Like” Scrapie from Bovine Classical and L-Type BSE in Ovine Transgenic Mice

“…Furthermore glycoforms proportions of BSE in sheep have only been determined from a very limited number of sources. A recent study of classical BSE in cattle showed large individual variations (∼20%) in the proportions of di-glycosylated PrP res [34].…”

Atypical Transmissible Spongiform Encephalopathies in Ruminants: A Challenge for Disease Surveillance and Control

“…44,45,134 These nuclei were also the structures where PrP d was detectable in the absence of lesions in preclinical BSE cases that had been first identified through herdculling schemes. 145,148,160 The typical BSE WB profile has a 3-band pattern with a clearly more prominent diglycosylated PrP res band, as compared with the monoglycosylated band ( Fig. 2A, C-type), 95 and was, therefore, distinct from those observed in most natural, classical scrapie cases.…”