PRP IN PATHOLOGY AND PATHOGENESIS IN SCRAPIE-INFECTED MICE

PrP accumulation in the brains of mice infected with scrapie takes sev eral different forms: amyloid plaques, widespread accumulation in neur opile, and perineuronal deposits. PrP is also sometimes detected withi n microglia and in or around astrocytes. There are dramatic and reprod ucible differences between scrapie strains in the relative prominence of these changes and their distribution in the brain. Depending on the scrapie strain, PrP pathology is targeted precisely to particular bra in areas, often showing a clear association with identifiable groups o f neurons. These results suggest that PrP changes are primarily associ ated with neurons, and that different scrapie strains recognize and se lectively replicate in different populations of neurons. Immunostainin g at the ultrastructural level demonstrates an association of PrP with neurite plasmalemma, around amyloid plaques, and in areas of widespre ad neuropile and perineuronal accumulation It is probable that PrP is encoded by the Sine gene, which controls the incubation period of scra pie in mice. Studies using the intraocular infection route show that t he Sirte gene controls the onset rather than the rate of replication, suggesting that PrP may be involved in cell-to-cell spread of infectio n. The accumulation of PrP at the surface of neurons is consistent wit h such a role.