Selective neuronal targeting in prion disease

The pattern of scrapie prion protein (PrPSc) accumulation in the brain is different for each prion strain. We tested whether the PrPSc deposition pattern is influenced by the Asn-linked oligosaccharides of PrPC in transgenic mice. Deletion of the first oligosaccharide altered PrPC trafficking and prevented infection with two prion strains. Deletion of the second did not alter PrPC trafficking, permitted infection with one prion strain, and had a profound effect on the PrPSc deposition pattern. Our data raise the possibility that glycosylation can modify the conformation of PrPC. Glycosylation could affect the affinity of PrPC for a particular conformer of PrPSc, thereby determining the rate of nascent PrPSc formation and the specific patterns of PrPSc deposition.