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Updated: Aug 14, 2026

Isolation of Soluble and Insoluble PrP Oligomers in the Normal Human Brain
Published on: October 3, 2012
Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease
Magdalini Polymenidou1, Katharina Stoeck, Markus Glatzel
1Institute of Neuropathology, University Hospital Zurich, Switzerland.
Background:
The molecular typing of sporadic Creutzfeldt-Jakob disease (CJD) is based on the size and glycoform ratio of protease-resistant prion protein (PrP(Sc)), and on PRNP haplotype. On digestion with proteinase K, type 1 and type 2 PrP(Sc) display unglycosylated core fragments of 21 kDa and 19 kDa, resulting from cleavage around amino acids 82 and 97, respectively.
Methods:
We generated anti-PrP monoclonal antibodies to epitopes immediately preceding the differential proteinase K cleavage sites. These antibodies, which were designated POM2 and POM12, recognise type 1, but not type 2, PrP(Sc).
Findings:
We studied 114 brain samples from 70 patients with sporadic CJD and three patients with variant CJD. Every patient classified as CJD type 2, and all variant CJD patients, showed POM2/POM12 reactivity in the cerebellum and other PrP(Sc)-rich brain areas, with a typical PrP(Sc) type 1 migration pattern.
Interpretation:
The regular coexistence of multiple PrP(Sc) types in patients with CJD casts doubts on the validity of electrophoretic PrP(Sc) mobilities as surrogates for prion strains, and questions the rational basis of current CJD classifications.
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