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A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques

The presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt–Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrP(D) type 1 (T1). Despit...

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Autores principales: Bayazid, Rabeah, Orru’, Christina, Aslam, Rabail, Cohen, Yvonne, Silva-Rohwer, Amelia, Lee, Seong-Ki, Occhipinti, Rossana, Kong, Qingzhong, Shetty, Shashirekha, Cohen, Mark L., Caughey, Byron, Schonberger, Lawrence B., Appleby, Brian S., Cali, Ignazio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166463/
https://www.ncbi.nlm.nih.gov/pubmed/37156880
http://dx.doi.org/10.1007/s00401-023-02581-1
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author Bayazid, Rabeah
Orru’, Christina
Aslam, Rabail
Cohen, Yvonne
Silva-Rohwer, Amelia
Lee, Seong-Ki
Occhipinti, Rossana
Kong, Qingzhong
Shetty, Shashirekha
Cohen, Mark L.
Caughey, Byron
Schonberger, Lawrence B.
Appleby, Brian S.
Cali, Ignazio
author_facet Bayazid, Rabeah
Orru’, Christina
Aslam, Rabail
Cohen, Yvonne
Silva-Rohwer, Amelia
Lee, Seong-Ki
Occhipinti, Rossana
Kong, Qingzhong
Shetty, Shashirekha
Cohen, Mark L.
Caughey, Byron
Schonberger, Lawrence B.
Appleby, Brian S.
Cali, Ignazio
author_sort Bayazid, Rabeah
collection PubMed
description The presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt–Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrP(D) type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrP(D) T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (p(GM)) or the white matter (p(WM)) of sCJD cases with the PrP 129MM genotype (sCJDMM). Prevalence of p(GM)- and p(WM)-CJD proved comparable and was estimated to be ~ 0.6% among sporadic prion diseases and ~ 1.1% among the sCJDMM group. Mean age at onset (61 and 68 years) and disease duration (~ 7 months) of p(WM)- and p(GM)-CJD did not differ significantly. PrP plaques were mostly confined to the cerebellar cortex in p(GM)-CJD, but were ubiquitous in p(WM)-CJD. Typing of resPrP(D) T1 showed an unglycosylated fragment of ~ 20 kDa (T1(20)) in p(GM)-CJD and sCJDMM1 patients, while a doublet of ~ 21–20 kDa (T1(21−20)) was a molecular signature of p(WM)-CJD in subcortical regions. In addition, conformational characteristics of p(WM)-CJD resPrP(D) T1 differed from those of p(GM)-CJD and sCJDMM1. Inoculation of p(WM)-CJD and sCJDMM1 brain extracts to transgenic mice expressing human PrP reproduced the histotype with PrP plaques only in mice challenged with p(WM)-CJD. Furthermore, T1(20) of p(WM)-CJD, but not T1(21), was propagated in mice. These data suggest that T1(21) and T1(20) of p(WM)-CJD, and T1(20) of sCJDMM1 are distinct prion strains. Further studies are required to shed light on the etiology of p-CJD cases, particularly those of T1(20) of the novel p(GM)-CJD subtype. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-023-02581-1.
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spelling pubmed-101664632023-05-09 A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques Bayazid, Rabeah Orru’, Christina Aslam, Rabail Cohen, Yvonne Silva-Rohwer, Amelia Lee, Seong-Ki Occhipinti, Rossana Kong, Qingzhong Shetty, Shashirekha Cohen, Mark L. Caughey, Byron Schonberger, Lawrence B. Appleby, Brian S. Cali, Ignazio Acta Neuropathol Original Paper The presence of amyloid kuru plaques is a pathological hallmark of sporadic Creutzfeldt–Jakob disease (sCJD) of the MV2K subtype. Recently, PrP plaques (p) have been described in the white matter of a small group of CJD (p-CJD) cases with the 129MM genotype and carrying resPrP(D) type 1 (T1). Despite the different histopathological phenotype, the gel mobility and molecular features of p-CJD resPrP(D) T1 mimic those of sCJDMM1, the most common human prion disease. Here, we describe the clinical features, histopathology, and molecular properties of two distinct PrP plaque phenotypes affecting the gray matter (p(GM)) or the white matter (p(WM)) of sCJD cases with the PrP 129MM genotype (sCJDMM). Prevalence of p(GM)- and p(WM)-CJD proved comparable and was estimated to be ~ 0.6% among sporadic prion diseases and ~ 1.1% among the sCJDMM group. Mean age at onset (61 and 68 years) and disease duration (~ 7 months) of p(WM)- and p(GM)-CJD did not differ significantly. PrP plaques were mostly confined to the cerebellar cortex in p(GM)-CJD, but were ubiquitous in p(WM)-CJD. Typing of resPrP(D) T1 showed an unglycosylated fragment of ~ 20 kDa (T1(20)) in p(GM)-CJD and sCJDMM1 patients, while a doublet of ~ 21–20 kDa (T1(21−20)) was a molecular signature of p(WM)-CJD in subcortical regions. In addition, conformational characteristics of p(WM)-CJD resPrP(D) T1 differed from those of p(GM)-CJD and sCJDMM1. Inoculation of p(WM)-CJD and sCJDMM1 brain extracts to transgenic mice expressing human PrP reproduced the histotype with PrP plaques only in mice challenged with p(WM)-CJD. Furthermore, T1(20) of p(WM)-CJD, but not T1(21), was propagated in mice. These data suggest that T1(21) and T1(20) of p(WM)-CJD, and T1(20) of sCJDMM1 are distinct prion strains. Further studies are required to shed light on the etiology of p-CJD cases, particularly those of T1(20) of the novel p(GM)-CJD subtype. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00401-023-02581-1. Springer Berlin Heidelberg 2023-05-08 2023 /pmc/articles/PMC10166463/ /pubmed/37156880 http://dx.doi.org/10.1007/s00401-023-02581-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Paper
Bayazid, Rabeah
Orru’, Christina
Aslam, Rabail
Cohen, Yvonne
Silva-Rohwer, Amelia
Lee, Seong-Ki
Occhipinti, Rossana
Kong, Qingzhong
Shetty, Shashirekha
Cohen, Mark L.
Caughey, Byron
Schonberger, Lawrence B.
Appleby, Brian S.
Cali, Ignazio
A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques
title A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques
title_full A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques
title_fullStr A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques
title_full_unstemmed A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques
title_short A novel subtype of sporadic Creutzfeldt–Jakob disease with PRNP codon 129MM genotype and PrP plaques
title_sort novel subtype of sporadic creutzfeldt–jakob disease with prnp codon 129mm genotype and prp plaques
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10166463/
https://www.ncbi.nlm.nih.gov/pubmed/37156880
http://dx.doi.org/10.1007/s00401-023-02581-1
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