Limits...
Beyond PrP9res) type 1/type 2 dichotomy in Creutzfeldt-Jakob disease.

Uro-Coste E, Cassard H, Simon S, Lugan S, Bilheude JM, Perret-Liaudet A, Ironside JW, Haik S, Basset-Leobon C, Lacroux C, Peoch' K, Streichenberger N, Langeveld J, Head MW, Grassi J, Hauw JJ, Schelcher F, Delisle MB, Andréoletti O - PLoS Pathog. (2008)

Bottom Line: However, since cases of CJD show co-occurrence of type 1 and type 2 PrP(res) in the brain, the basis of this classification system and its relationship to agent strain are under discussion.In 30% of cases, both type 1 and type 2 PrP(res) were identified.Despite this, the other two biochemical assays found that PrP(Sc) from an individual patient demonstrated uniform biochemical properties.

View Article: PubMed Central - PubMed

Affiliation: INSERM U858, Institut de Médecine Moléculaire de Rangueil and Service d'Anatomie Pathologique et Histologie-Cytologie, C.H.U. Rangueil, Toulouse, France.

ABSTRACT
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 (PrP(res)) identified on Western blotting (type 1 or type 2). These biochemically distinct PrP(res) types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrP(res) in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrP(res) and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrP(Sc)) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrP(res) were identified. Despite this, the other two biochemical assays found that PrP(Sc) from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrP(Sc) 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 PrP(res) pattern. The identification of four different PrP(Sc) biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrP(res) isoform provides an alternative biochemical definition of PrP(Sc) diversity and new insight in the perception of Human TSE agents variability.

Show MeSH

Related in: MedlinePlus

PK Resistance ELISA in Frontal Cortex from sCJD and French or UK iCJD (Growth Hormone and Dura Mater Cases).sCJD (solid line) and i-CJD (dashed line) frontal cortex samples were investigated by PK resistance assay. (A) MM1 sCJD cases (open circles, hexagons and squares), MM1 iCJD UK dura mater cases (open diamonds), MM1 French GH cases (open triangles). (B) MV2 sCJD cases (filled circles, hexagons and squares) and MV2 UK GH case (filled triangles). (C) MV1 sCJD (open circles, diamonds and squares) and MV1 French GH (open triangles) cases. (D) VV2 sCJD (filled circles and hexagons) and VV2 UK GH (filled triangles) cases. (E) VV1 sCJD case (open circles) and VV1 dura mater French case (open triangles). (F) MM2 sCJD cases (filled circles and triangles).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2279301&req=5

ppat-1000029-g004: PK Resistance ELISA in Frontal Cortex from sCJD and French or UK iCJD (Growth Hormone and Dura Mater Cases).sCJD (solid line) and i-CJD (dashed line) frontal cortex samples were investigated by PK resistance assay. (A) MM1 sCJD cases (open circles, hexagons and squares), MM1 iCJD UK dura mater cases (open diamonds), MM1 French GH cases (open triangles). (B) MV2 sCJD cases (filled circles, hexagons and squares) and MV2 UK GH case (filled triangles). (C) MV1 sCJD (open circles, diamonds and squares) and MV1 French GH (open triangles) cases. (D) VV2 sCJD (filled circles and hexagons) and VV2 UK GH (filled triangles) cases. (E) VV1 sCJD case (open circles) and VV1 dura mater French case (open triangles). (F) MM2 sCJD cases (filled circles and triangles).

Mentions: Striking differences were observed in the PrPSc properties between the different iCJD cases and all four groups relying on PrPSc signatures observed in sCJD cases were identified (Table 1, and Figures 3B and 4).


Beyond PrP9res) type 1/type 2 dichotomy in Creutzfeldt-Jakob disease.

Uro-Coste E, Cassard H, Simon S, Lugan S, Bilheude JM, Perret-Liaudet A, Ironside JW, Haik S, Basset-Leobon C, Lacroux C, Peoch' K, Streichenberger N, Langeveld J, Head MW, Grassi J, Hauw JJ, Schelcher F, Delisle MB, Andréoletti O - PLoS Pathog. (2008)

PK Resistance ELISA in Frontal Cortex from sCJD and French or UK iCJD (Growth Hormone and Dura Mater Cases).sCJD (solid line) and i-CJD (dashed line) frontal cortex samples were investigated by PK resistance assay. (A) MM1 sCJD cases (open circles, hexagons and squares), MM1 iCJD UK dura mater cases (open diamonds), MM1 French GH cases (open triangles). (B) MV2 sCJD cases (filled circles, hexagons and squares) and MV2 UK GH case (filled triangles). (C) MV1 sCJD (open circles, diamonds and squares) and MV1 French GH (open triangles) cases. (D) VV2 sCJD (filled circles and hexagons) and VV2 UK GH (filled triangles) cases. (E) VV1 sCJD case (open circles) and VV1 dura mater French case (open triangles). (F) MM2 sCJD cases (filled circles and triangles).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2279301&req=5

ppat-1000029-g004: PK Resistance ELISA in Frontal Cortex from sCJD and French or UK iCJD (Growth Hormone and Dura Mater Cases).sCJD (solid line) and i-CJD (dashed line) frontal cortex samples were investigated by PK resistance assay. (A) MM1 sCJD cases (open circles, hexagons and squares), MM1 iCJD UK dura mater cases (open diamonds), MM1 French GH cases (open triangles). (B) MV2 sCJD cases (filled circles, hexagons and squares) and MV2 UK GH case (filled triangles). (C) MV1 sCJD (open circles, diamonds and squares) and MV1 French GH (open triangles) cases. (D) VV2 sCJD (filled circles and hexagons) and VV2 UK GH (filled triangles) cases. (E) VV1 sCJD case (open circles) and VV1 dura mater French case (open triangles). (F) MM2 sCJD cases (filled circles and triangles).
Mentions: Striking differences were observed in the PrPSc properties between the different iCJD cases and all four groups relying on PrPSc signatures observed in sCJD cases were identified (Table 1, and Figures 3B and 4).

Bottom Line: However, since cases of CJD show co-occurrence of type 1 and type 2 PrP(res) in the brain, the basis of this classification system and its relationship to agent strain are under discussion.In 30% of cases, both type 1 and type 2 PrP(res) were identified.Despite this, the other two biochemical assays found that PrP(Sc) from an individual patient demonstrated uniform biochemical properties.

View Article: PubMed Central - PubMed

Affiliation: INSERM U858, Institut de Médecine Moléculaire de Rangueil and Service d'Anatomie Pathologique et Histologie-Cytologie, C.H.U. Rangueil, Toulouse, France.

ABSTRACT
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 (PrP(res)) identified on Western blotting (type 1 or type 2). These biochemically distinct PrP(res) types have been considered to represent potential distinct prion strains. However, since cases of CJD show co-occurrence of type 1 and type 2 PrP(res) in the brain, the basis of this classification system and its relationship to agent strain are under discussion. Different brain areas from 41 sCJD and 12 iatrogenic CJD (iCJD) cases were investigated, using Western blotting for PrP(res) and two other biochemical assays reflecting the behaviour of the disease-associated form of the prion protein (PrP(Sc)) under variable PK digestion conditions. In 30% of cases, both type 1 and type 2 PrP(res) were identified. Despite this, the other two biochemical assays found that PrP(Sc) from an individual patient demonstrated uniform biochemical properties. Moreover, in sCJD, four distinct biochemical PrP(Sc) 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 PrP(res) pattern. The identification of four different PrP(Sc) biochemical subgroups in sCJD and iCJD, irrespective of the PRNP polymorphism at codon 129 and the PrP(res) isoform provides an alternative biochemical definition of PrP(Sc) diversity and new insight in the perception of Human TSE agents variability.

Show MeSH
Related in: MedlinePlus