For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
330
views
22
references
 Top references
cited by
17
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      481
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Characteristic CSF Prion Seeding Efficiency in Humans with Prion Diseases

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references22

          • Record: found
          • Abstract: found
          • Article: not found

          Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects.

          P Parchi, A. Giese, S Capellari … (1999)
          Phenotypic heterogeneity in sporadic Creutzfeldt-Jakob disease (sCJD) is well documented, but there is not yet a systematic classification of the disease variants. In a previous study, we showed that the polymorphic codon 129 of the prion protein gene (PRNP), and two types of protease-resistant prion protein (PrP(Sc)) with distinct physicochemical properties, are major determinants of these variants. To define the full spectrum of variants, we have examined a series of 300 sCJD patients. Clinical features, PRNP genotype, and PrP(Sc) properties were determined in all subjects. In 187, we also studied neuropathological features and immunohistochemical pattern of PrP(Sc) deposition. Seventy percent of subjects showed the classic CJD phenotype, PrP(Sc) type 1, and at least one methionine allele at codon 129; 25% of cases displayed the ataxic and kuru-plaque variants, associated to PrP(Sc) type 2, and valine homozygosity or heterozygosity at codon 129, respectively. Two additional variants, which included a thalamic form of CJD and a phenotype characterized by prominent dementia and cortical pathology, were linked to PrP(Sc) type 2 and methionine homozygosity. Finally, a rare phenotype characterized by progressive dementia was linked to PrP(Sc) type 1 and valine homozygosity. The present data demonstrate the existence of six phenotypic variants of sCJD. The physicochemical properties of PrP(Sc) in conjunction with the PRNP codon 129 genotype largely determine this phenotypic variability, and allow a molecular classification of the disease variants.
          Article 0 comments Cited 156 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Genetic prion disease: the EUROCJD experience.

            Matthew Bishop, Eva Mitrova, Francis Collins … (2005)
            A total of 10-15% of human transmissible spongiform encephalopathies (TSEs) or prion diseases are characterised by disease-specific mutations in the prion protein gene (PRNP). We examined the phenotype, distribution, and frequency of genetic TSEs (gTSEs) in different countries/geographical regions. We collected standardised data on gTSEs between 1993 and 2002 in the framework of the EUROCJD collaborative surveillance project. Our results show that clinicopathological phenotypes include genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Sträussler-Scheinker disease (GSS). Genetic TSE patients with insert mutation in the PRNP represent a separate group. Point and insertional mutations in the PRNP gene varies significantly in frequency between countries. The commonest mutation is E200K. Absence of a positive family history is noted in a significant proportion of cases in all mutation types (12-88%). FFI and GSS patients develop disease earlier than gCJD. Base pair insertions associated with the Creutzfeldt-Jakob disease (CJD) phenotype, GSS, and FFI cases have a longer duration of illness compared to cases with point mutations and gCJD. Cerebrospinal fluid 14-3-3 immunoassay, EEG, and MRI brain scan are useful in the diagnosis of CJD with point mutations, but are less sensitive in the other forms. Given the low prevalence of family history, the term "gTSE" is preferable to "familial TSE". Application of genetic screening in clinical practice has the advantage of early diagnosis and may lead to the identification of a risk of a TSE.
            Article 0 comments Cited 118 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Sporadic and familial CJD: classification and characterisation.

              S. Chen, Wenquan Zou, Pierluigi Gambetti … (2002)
              Prion diseases are unique transmissible neurodegenerative diseases that have diverse phenotypes and can be familial, sporadic, or acquired by infection. Recent findings indicate that the PrP genotype and the PrP(Sc) type have a major influence on the disease phenotype in both sporadic and familial human prion diseases. This review attempts to classify and characterise sporadic and familial Creutzfeldt-Jakob disease (CJD) as a function of these two disease determinants. Based on the genotype at codon 129 on both PRNP alleles, the size of protease resistant PrP(Sc) fragments and disease phenotype, we divide sporadic CJD into six subtypes: sCJDMM1/sCJDMV1, sCJDVV2, sCJDMV2, sCJDMM2, sCJDVV1, and sporadic fatal insomnia (sFI). Familial CJD is classified into many haplotypes based on the PRNP mutation and codon 129 (and other polymorphic codons) on the mutant allele. The clinical and pathological features are summarised for each sporadic CJD subtype and familial CJD haplotype.
              Article 0 comments Cited 92 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Matthias Schmitz: +49-551-3910454 , +49-551-397020 , matthias.schmitz@med.uni-goettingen.de
                Journal
                Journal ID (nlm-ta): Mol Neurobiol
                Journal ID (iso-abbrev): Mol. Neurobiol
                Title: Molecular Neurobiology
                Publisher: Springer US (Boston )
                ISSN (Print): 0893-7648
                ISSN (Electronic): 1559-1182
                Publication date (Electronic): 9 May 2014
                Publication date PMC-release: 9 May 2014
                Publication date (Print): 2015
                Volume: 51
                Pages: 396-405
                Affiliations
                [ ]Department of Neurology, Clinical Dementia Center, University Medical Center Göttingen and German Center for Neurodegenerative Diseases (DZNE) – site Göttingen, Robert-Koch-Str. 40, 37075 Göttingen, Germany
                [ ]Slovak Medical University, Limbova 14, 833-03 Bratislava, Slovakia
                [ ]Prionics AG, 8952 Schlieren, Switzerland
                Article
                Publisher ID: 8709
                DOI: 10.1007/s12035-014-8709-6
                PMC ID: 4309904
                PubMed ID: 24809690
                SO-VID: 4bbd9c9d-9d78-4bc0-8198-c4cc6f0f3a62
                Copyright © © The Author(s) 2014
                License:

                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.

                History
                Date received : 17 February 2014
                Date accepted : 9 April 2014
                Categories
                Subject: Article
                Custom metadata
                issue-copyright-statement © Springer Science+Business Media New York 2015

                ScienceOpen disciplines: Neurosciences
                Keywords: cerebrospinal fluid,creutzfeldt-jakob disease,premortem test,prion protein,real-time quaking-induced conversion assay
                Data availability:
                ScienceOpen disciplines: Neurosciences
                Keywords: cerebrospinal fluid, creutzfeldt-jakob disease, premortem test, prion protein, real-time quaking-induced conversion assay

                Comments

                Comment on this article

                scite_

                Similar content481

                See all similar

                Cited by51

                See all cited by

                Most referenced authors754

                See all reference authors