PrP accumulation in the brains of mice infected with
scrapie takes several different forms:
amyloid plaques, widespread accumulation in neuropile, and perineuronal deposits. PrP is also sometimes detected within microglia and in or around astrocytes. There are dramatic and reproducible 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 brain areas, often showing a clear association with identifiable groups of neurons. These results suggest that PrP changes are primarily associated with neurons, and that different
scrapie strains recognize and selectively replicate in different populations of neurons. Immunostaining at the ultrastructural level demonstrates an association of PrP with neurite plasmalemma, around
amyloid plaques, and in areas of widespread neuropile and perineuronal accumulation. It is probable that PrP is encoded by the
Sinc gene, which controls the incubation period of
scrapie in mice. Studies using the intraocular
infection route show that the
Sinc gene controls the onset rather than the rate of replication, suggesting that PrP may be involved in cell-to-cell spread of
infection. The accumulation of PrP at the surface of neurons is consistent with such a role.