The molecular pathology of scrapie and the biological basis of lesion targeting.

Strains of scrapie virus can only be distinguished from the incubation period and neuropathology of the disease they induce in mice of different Sinc genotypes. There are two main aspects of the neuropathology: a spongiosis or degenerative vacuolation associated with the replication of virus, and cerebral amyloid plaques. The relationship between these two is unclear - they can occupy topographically quite different centres in the CNS and the timing of their occurrence is different. Surprisingly this is also the case using the very precise targeting provided by the intraocular infection route. Here the earliest spongiosis is very localised into the primary and secondary projections from the retina, but plaques, when they occur, occupy quite different sites. The relationship between plaques and spongy degeneration is probably a neuroanatomical one, similar to that suggested between plaques and tangle-bearing neurons in Alzheimer's disease. A third aspect of the pathology is the occurrence of SAF in negative-stained E.M. preparations, formed from the aggregation of a sialoglycoprotein called PrP or SAF-protein. Immunolabelling of plaques with antisera to SAF protein shows as yet that there is no antigenic variation in the protein prepared from different scrapie models with different strains of the virus based on available reagents. Strain variation is only recognised on biological criteria; as yet, there are no independent molecular markers or in vitro tests which can account for the biological variation.