Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease.
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).


RESULTS
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.


CONCLUSIONS
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.
Polymenidou
Magdalini
M
Institute of Neuropathology, University Hospital Zurich, Switzerland.
Stoeck
Katharina
K
Glatzel
Markus
M
Vey
Martin
M
Bellon
Anne
A
Aguzzi
Adriano
A
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification / Q000378:metabolism*; D003720:Densitometry / Q000379:methods; D004305:Dose-Response Relationship, Drug; D019286:Endopeptidase K / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018620:PrPSc Proteins / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D020349:Surface Plasmon Resonance / Q000379:methods
D000911:Antibodies, Monoclonal; D000939:Epitopes; D018620:PrPSc Proteins; D019286:Endopeptidase K