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From: TSS ()
Subject: Coexistence of multiple PrPSc types in individuals with Creutzfeldt-Jakob disease
Date: November 18, 2005 at 7:56 am PST

TSS
Coexistence of multiple PrPSc types in individuals with CJD
Fri Nov 18, 2005 10:05
70.110.89.13

Lancet Neurology 2005; 4:805-814

DOI:10.1016/S1474-4422(05)70225-8

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

Magdalini Polymenidou a, Katharina Stoeck a, Markus Glatzel a b, Martin Vey c, Anne Bellon c and Adriano Aguzzi a

Summary
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.

Affiliations

a Institute of Neuropathology, University Hospital Zurich, Switzerland
b Present address: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
c ZLB Behring, Marburg, Germany

Correspondence to: Dr Adriano Aguzzi, Institute of Neuropathology, University Hospital of Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland

http://www.thelancet.com/journals/laneur/article/PIIS1474442205702258/abstract

what i been saying for years, that the diagnostic criteria differentiating between the nvCJD (i.e. 'the chosen ones') and the sCJD (i.e. 'the forgotten ones') has been terribly flawed from the beginning. ....

TSS



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