PrP Sc spreading patterns in the brain of sheep linked to different prion types

Abstract

Scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (BSE) and Creutzfeldt-Jakob disease in humans. According to the prion hypothesis, the pathological isoform (PrP Sc) of the cellular prion protein (PrP c) comprises the essential, if not exclusive, component of the transmissible agent. Currently, two types of scrapie disease are known - classical and atypical/Nor98 scrapie. In the present study we examine 24 cases of classical and 25 cases of atypical/Nor98 scrapie with the sensitive PET blot method and validate the results with conventional immunohistochemistry. The sequential detection of PrP Sc aggregates in the CNS of classical scrapie sheep implies that after neuroinvasion a spread from spinal cord and obex to the cerebellum, diencephalon and frontal cortex via the rostral brainstem takes place. We categorize the spread of PrP Sc into four stages: the CNS entry stage, the brainstem stage, the cruciate sulcus stage and finally the basal ganglia stage. Such a sequential development of PrP Sc was not detectable upon analysis of the present atypical/Nor98 scrapie cases. PrP Sc distribution in one case of atypical/Nor98 scrapie in a presumably early disease phase suggests that the spread of PrP Sc aggregates starts in the di- or telencephalon. In addition to the spontaneous generation of PrP Sc, an uptake of the infectious agent into the brain, that bypasses the brainstem and starts its accumulation in the thalamus, needs to be taken into consideration for atypical/Nor98 scrapie. © 2011 Wemheuer et al; licensee BioMed Central Ltd.