Regional mapping of prion proteins in brain

Scrapie is characterized by the accumulation of a protease-resistant isoform of the prion protein PrP^Sc. Limited proteolysis and chaotropes were used to map the distribution of PrP^Sc in cryostat sections of scrapie-infected brain blotted onto nitrocellulose membranes, designated histoblots. Proteolysis was omitted in order to map the cellular isoform of the prion protein (PrP^C) in uninfected brains. Compared with immunohistochemistry, histoblots increased the sensitivity for PrP^Sc detection and showed different patterns of PrP^Sc accumulation. In Syrian hamsters with Sc237 scrapie, the most intense PrP^Sc signals occurred in sites with relatively little PrP^C, suggesting that aberrant localization of prion protein may be an important feature in the pathogenesis of prion diseases. Immunostaining of PrP^Sc in white-matter tracts suggested that prions spread along neuroanatomical pathways. PrP^Sc immunostaining in histoblots was quantitated by densitometry, permitting assessment of the extent of PrP^Sc accumulation within specific structures. Histoblots were also useful in localizing PrP^CJD and β/A4-amyloid peptide in the brains of patients with Creutzfeldt-Jakob disease and Alzheimer disease, respectively.