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During the last stage of infection in the experimental scrapie-infected hamster model, light microscopy reveals typical immunostaining of PrPsc in the subependymal region and at the apical ependymal cell borders. Whereas the subependymal immuno-staining is known to originate from extracellular amyloid filaments and residual membranes of astrocytes as constituents of plaque-like structures, the ultrastructural correlate of the supraependymal PrPsc staining remains uncertain. To decipher this apical PrPsc immunopositivity and subsequently the ependymocyte-scrapie agent interaction, we employed highly sensitive immuno-electron microscopy for detecting PrPsc in 263K scrapie-infected hamster brains. The results revealed the supraependymal PrPsc signal to be correlated not only with extracellular accumulation of amyloid filaments, but also with three distinct ependymal cell structures: (1) morphologically intact or altered microvilli associated with filaments, (2) the ependymal cell cytoplasm in proximity of apical cell membrane, and (3) intracytoplasmic organelles such as endosomes and lysosomal-like structures. These findings suggest a strong ependymotrope feature of the scrapie agent and recapitulate several aspects of the cell-prion interaction leading to the formation and production of PrPsc amyloid filaments. Our data demonstrate that in addition to neurons and astrocytes, ependymocytes constitute a new cellular target for the scrapie agent. In contrast, the absence of PrPsc labeling in choroid plexus and brain vascular endothelial cells indicates that these cells are not susceptible to the infection and may inhibit passage of the infectious agent across the blood-brain barrier.

This update concerns human and ruminant transmissible spongiform subacute encephalopathies (TSSE). The latest data on variant Creutzfeldt-Jakob disease confirm that new cases are less frequent than feared some years ago, but subclinical carriers could be a source of iatrogenic infection. The macaque is a good model of human oral transmission of bovine spongiform encephalopathy (BSE). The latest data on BSE in Europe confirm the effectiveness of precautionary measures taken in 1996 and 2000. Concerns in other ruminants include a chronic wasting disease of Cervidae in North America, the discovery of a BSE-like agent associated with natural scrapie in a French goat, maternal transmission of natural scrapie in sheep, with an exceptionally short incubation period (6.5 months), and doubts over the efficacy of genetic selection for combating ovine scrapie (atypical cases in " resistant " sheep, especially with the scrapie strain Nor 98 in Europe). These data demonstrate the value of active European surveillance of scrapie in small ruminants.

SIR, – One of the concerns about BSE is the potential presence of the agent in small ruminants, sheep and goats, as well as cattle. With the objective of documenting this, seven French laboratories have analysed 438 brain samples from confirmed cases of TSE in sheep and goats. These comprised