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Updated: Sep 19, 2026

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain
Published on: October 3, 2012
Evidence for multiple prion conformers in natural scrapie isolates
Morikazu Imamura1, Kohtaro Miyazawa2, Hiroyuki Okada3
1Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Abstract:
Prion strains in infected animals may exist as heterogeneous populations composed of a major prion conformer responsible for the dominant disease phenotype and minor conformers that are phenotypically silent or difficult to detect. However, the presence and biological significance of such minor conformers in natural prion isolates remain poorly understood. Identifying and characterizing these hidden substrains is important for understanding prion strain diversity and for assessing potential transmission risks to humans and livestock. In this study, we utilized a modified protein misfolding cyclic amplification (PMCA) method to detect substrains within classical scrapie isolates. Our analysis provided evidence consistent with the coexistence of multiple prion conformers, including previously unrecognized conformers, within single prion isolates. Furthermore, we observed changes in the detectable substrain composition during passages in animal hosts. These findings support the idea that scrapie prion populations can contain diverse conformers and that changes in detectable conformer populations during passage may contribute to the overall diversity of scrapie prions.
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