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Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases

The development of in vitro amplification systems allows detecting femtomolar amounts of prion protein scrapie (PrP(Sc)) in human cerebrospinal fluid (CSF). We performed a CSF study to determine the effects of prion disease type, codon 129 genotype, PrP(Sc) type, and other disease-related factors on...

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Autores principales: Cramm, Maria, Schmitz, Matthias, Karch, André, Zafar, Saima, Varges, Daniela, Mitrova, Eva, Schroeder, Bjoern, Raeber, Alex, Kuhn, Franziska, Zerr, Inga
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309904/
https://www.ncbi.nlm.nih.gov/pubmed/24809690
http://dx.doi.org/10.1007/s12035-014-8709-6
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author Cramm, Maria
Schmitz, Matthias
Karch, André
Zafar, Saima
Varges, Daniela
Mitrova, Eva
Schroeder, Bjoern
Raeber, Alex
Kuhn, Franziska
Zerr, Inga
author_facet Cramm, Maria
Schmitz, Matthias
Karch, André
Zafar, Saima
Varges, Daniela
Mitrova, Eva
Schroeder, Bjoern
Raeber, Alex
Kuhn, Franziska
Zerr, Inga
author_sort Cramm, Maria
collection PubMed
description The development of in vitro amplification systems allows detecting femtomolar amounts of prion protein scrapie (PrP(Sc)) in human cerebrospinal fluid (CSF). We performed a CSF study to determine the effects of prion disease type, codon 129 genotype, PrP(Sc) type, and other disease-related factors on the real-time quaking-induced conversion (RT-QuIC) response. We analyzed times to 10,000 relative fluorescence units, areas under the curve and the signal maximum of RT-QuIC response as seeding parameters of interest. Interestingly, type of prion disease (sporadic vs. genetic) and the PRNP mutation (E200K vs. V210I and FFI), codon 129 genotype, and PrP(Sc) type affected RT-QuIC response. In genetic forms, type of mutation showed the strongest effect on the observed outcome variables. In sporadic CJD, MM1 patients displayed a higher RT-QuIC signal maximum compared to MV1 and VV1. Age and gender were not associated with RT-QuIC signal, but patients with a short disease course showed a higher seeding efficiency of the RT-QuIC response. This study demonstrated that PrP(Sc) characteristics in the CSF of human prion disease patients are associated with disease subtypes and rate of decline as defined by disease duration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12035-014-8709-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-43099042015-02-02 Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases Cramm, Maria Schmitz, Matthias Karch, André Zafar, Saima Varges, Daniela Mitrova, Eva Schroeder, Bjoern Raeber, Alex Kuhn, Franziska Zerr, Inga Mol Neurobiol Article The development of in vitro amplification systems allows detecting femtomolar amounts of prion protein scrapie (PrP(Sc)) in human cerebrospinal fluid (CSF). We performed a CSF study to determine the effects of prion disease type, codon 129 genotype, PrP(Sc) type, and other disease-related factors on the real-time quaking-induced conversion (RT-QuIC) response. We analyzed times to 10,000 relative fluorescence units, areas under the curve and the signal maximum of RT-QuIC response as seeding parameters of interest. Interestingly, type of prion disease (sporadic vs. genetic) and the PRNP mutation (E200K vs. V210I and FFI), codon 129 genotype, and PrP(Sc) type affected RT-QuIC response. In genetic forms, type of mutation showed the strongest effect on the observed outcome variables. In sporadic CJD, MM1 patients displayed a higher RT-QuIC signal maximum compared to MV1 and VV1. Age and gender were not associated with RT-QuIC signal, but patients with a short disease course showed a higher seeding efficiency of the RT-QuIC response. This study demonstrated that PrP(Sc) characteristics in the CSF of human prion disease patients are associated with disease subtypes and rate of decline as defined by disease duration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12035-014-8709-6) contains supplementary material, which is available to authorized users. Springer US 2014-05-09 2015 /pmc/articles/PMC4309904/ /pubmed/24809690 http://dx.doi.org/10.1007/s12035-014-8709-6 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Article
Cramm, Maria
Schmitz, Matthias
Karch, André
Zafar, Saima
Varges, Daniela
Mitrova, Eva
Schroeder, Bjoern
Raeber, Alex
Kuhn, Franziska
Zerr, Inga
Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases
title Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases
title_full Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases
title_fullStr Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases
title_full_unstemmed Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases
title_short Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases
title_sort characteristic csf prion seeding efficiency in humans with prion diseases
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4309904/
https://www.ncbi.nlm.nih.gov/pubmed/24809690
http://dx.doi.org/10.1007/s12035-014-8709-6
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