Beyond PrP res type 1/type 2 dichotomy in Creutzfeldt-Jakob disease.
Sporadic Creutzfeldt-Jakob disease (sCJD) cases are currently subclassified according to the methionine/valine polymorphism at codon 129 of the PRNP gene and the proteinase K (PK) digested abnormal prion protein (PrPres)identified on Western blotting (type 1 or type 2). These biochemically distinct PrPres types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrPres in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain are as from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrPres and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrPSc) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrPres were identified. Despite this, the other two biochemical assays found that PrPSc from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrPSc subgroups were identified that correlated with the current sCJD clinico-pathological classification. In iCJD, four similar biochemical clusters were observed, but these did not correlate to any particular PRNP 129 polymorphism or western blot PrPres pattern. The identification of four different PrPSc biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrPres isoform provides an alternative biochemical definition of PrPSc diversity and new insight in the perception of Human TSE agents variability.
Uro-Coste
Emmanuelle
E
INSERM U858, Institut de Médecine Moléculaire de Rangueil and Service d'Anatomie Pathologique et Histologie-Cytologie, C.H.U. Rangueil, Toulouse, France.
Cassard
Hervé
H
Simon
Stéphanie
S
Lugan
Séverine
S
Bilheude
Jean-Marc
JM
Perret-Liaudet
Armand
A
Ironside
James W
JW
Haik
Stéphane
S
Basset-Leobon
Christelle
C
Lacroux
Caroline
C
Peoch
Katell
K
Streichenberger
Nathalie
N
Langeveld
Jan
J
Head
Mark W
MW
Grassi
Jacques
J
Hauw
Jean-Jacques
JJ
Schelcher
Francois
F
Delisle
Marie Bernadette
MB
Andréoletti
Olivier
O
D001681:Biological Assay; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification* / Q000378:metabolism*; D006801:Humans; D018620:PrPSc Proteins / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000378:metabolism; D013045:Species Specificity
D018620:PrPSc Proteins; D020033:Protein Isoforms