NR ATXI
AU Polymenidou,M.; Stoeck,K.; Glatzel,M.; Vey,M.; Bellon,A.; Aguzzi,A.
TI Coexistence of multiple PrPsc types in individuals with Creutzfeldt-Jakob disease
QU Lancet Neurology 2005 Dec; 4(12): 805-14
KI Lancet Neurol. 2005 Dec;4(12):788-9. PMID: 16297832
ER Lancet Neurol. 2005 Dec;4(12):795
PT journal article
AB 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.
MH Antibodies, Monoclonal/immunology/metabolism; Blotting, Western/methods; Brain/drug effects/*metabolism/pathology; Comparative Study; Creutzfeldt-Jakob Syndrome/classification/*metabolism; Densitometry/methods; Dose-Response Relationship, Drug; Endopeptidase K/pharmacology; Enzyme-Linked Immunosorbent Assay/methods; Epitope Mapping/methods; Epitopes/immunology/metabolism; Female; Humans; Hydrogen-Ion Concentration; Immunohistochemistry/methods; Male; PrPsc Proteins/classification/immunology/*metabolism; Protein Structure, Tertiary/physiology; Research Support, Non-U.S. Gov't; Surface Plasmon Resonance/methods
AD Institute of Neuropathology, University Hospital Zürich, Switzerland.
SP englisch
PO England