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Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes

In the human prion disease Creutzfeldt-Jakob disease (CJD), different CJD neuropathological subtypes are defined by the presence in normal prion protein (PrP(C)) of a methionine or valine at residue 129, by the molecular mass of the infectious prion protein PrP(Sc), by the pattern of PrP(Sc) deposit...

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Autores principales: Ward, Anne, Hollister, Jason R., McNally, Kristin, Ritchie, Diane L., Zanusso, Gianluigi, Priola, Suzette A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285538/
https://www.ncbi.nlm.nih.gov/pubmed/32517816
http://dx.doi.org/10.1186/s40478-020-00958-x
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author Ward, Anne
Hollister, Jason R.
McNally, Kristin
Ritchie, Diane L.
Zanusso, Gianluigi
Priola, Suzette A.
author_facet Ward, Anne
Hollister, Jason R.
McNally, Kristin
Ritchie, Diane L.
Zanusso, Gianluigi
Priola, Suzette A.
author_sort Ward, Anne
collection PubMed
description In the human prion disease Creutzfeldt-Jakob disease (CJD), different CJD neuropathological subtypes are defined by the presence in normal prion protein (PrP(C)) of a methionine or valine at residue 129, by the molecular mass of the infectious prion protein PrP(Sc), by the pattern of PrP(Sc) deposition, and by the distribution of spongiform change in the brain. Heterozygous cases of CJD potentially add another layer of complexity to defining CJD subtypes since PrP(Sc) can have either a methionine (PrP(Sc)-M129) or valine (PrP(Sc)-V129) at residue 129. We have recently demonstrated that the relative amount of PrP(Sc)-M129 versus PrP(Sc)-V129, i.e. the PrP(Sc) allotype ratio, varies between heterozygous CJD cases. In order to determine if differences in PrP(Sc) allotype correlated with different disease phenotypes, we have inoculated 10 cases of heterozygous CJD (7 sporadic and 3 iatrogenic) into two transgenic mouse lines overexpressing PrP(C) with a methionine at codon 129. In one case, brain-region specific differences in PrP(Sc) allotype appeared to correlate with differences in prion disease transmission and phenotype. In the other 9 cases inoculated, the presence of PrP(Sc)-V129 was associated with plaque formation but differences in PrP(Sc) allotype did not consistently correlate with disease incubation time or neuropathology. Thus, while the PrP(Sc) allotype ratio may contribute to diverse prion phenotypes within a single brain, it does not appear to be a primary determinative factor of disease phenotype.
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spelling pubmed-72855382020-06-10 Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes Ward, Anne Hollister, Jason R. McNally, Kristin Ritchie, Diane L. Zanusso, Gianluigi Priola, Suzette A. Acta Neuropathol Commun Research In the human prion disease Creutzfeldt-Jakob disease (CJD), different CJD neuropathological subtypes are defined by the presence in normal prion protein (PrP(C)) of a methionine or valine at residue 129, by the molecular mass of the infectious prion protein PrP(Sc), by the pattern of PrP(Sc) deposition, and by the distribution of spongiform change in the brain. Heterozygous cases of CJD potentially add another layer of complexity to defining CJD subtypes since PrP(Sc) can have either a methionine (PrP(Sc)-M129) or valine (PrP(Sc)-V129) at residue 129. We have recently demonstrated that the relative amount of PrP(Sc)-M129 versus PrP(Sc)-V129, i.e. the PrP(Sc) allotype ratio, varies between heterozygous CJD cases. In order to determine if differences in PrP(Sc) allotype correlated with different disease phenotypes, we have inoculated 10 cases of heterozygous CJD (7 sporadic and 3 iatrogenic) into two transgenic mouse lines overexpressing PrP(C) with a methionine at codon 129. In one case, brain-region specific differences in PrP(Sc) allotype appeared to correlate with differences in prion disease transmission and phenotype. In the other 9 cases inoculated, the presence of PrP(Sc)-V129 was associated with plaque formation but differences in PrP(Sc) allotype did not consistently correlate with disease incubation time or neuropathology. Thus, while the PrP(Sc) allotype ratio may contribute to diverse prion phenotypes within a single brain, it does not appear to be a primary determinative factor of disease phenotype. BioMed Central 2020-06-09 /pmc/articles/PMC7285538/ /pubmed/32517816 http://dx.doi.org/10.1186/s40478-020-00958-x Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ward, Anne
Hollister, Jason R.
McNally, Kristin
Ritchie, Diane L.
Zanusso, Gianluigi
Priola, Suzette A.
Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes
title Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes
title_full Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes
title_fullStr Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes
title_full_unstemmed Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes
title_short Transmission characteristics of heterozygous cases of Creutzfeldt-Jakob disease with variable abnormal prion protein allotypes
title_sort transmission characteristics of heterozygous cases of creutzfeldt-jakob disease with variable abnormal prion protein allotypes
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285538/
https://www.ncbi.nlm.nih.gov/pubmed/32517816
http://dx.doi.org/10.1186/s40478-020-00958-x
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