Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease
M Polymenidou, K Stoeck, M Glatzel, M Vey… - The Lancet …, 2005 - thelancet.com
M Polymenidou, K Stoeck, M Glatzel, M Vey, A Bellon, A Aguzzi
The Lancet Neurology, 2005•thelancet.comBackground 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 …
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 …
Background
The molecular typing of sporadic Creutzfeldt-Jakob disease (CJD) is based on the size and glycoform ratio of protease-resistant prion protein (PrPSc), and on PRNP haplotype. On digestion with proteinase K, type 1 and type 2 PrPSc 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, PrPSc.
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 PrPSc-rich brain areas, with a typical PrPSc type 1 migration pattern.
Interpretation
The regular coexistence of multiple PrPSc types in patients with CJD casts doubts on the validity of electrophoretic PrPSc mobilities as surrogates for prion strains, and questions the rational basis of current CJD classifications.
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