Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785038447799435264 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10166463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT bayazidrabeah anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT orruchristina anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT aslamrabail anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT cohenyvonne anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT silvarohweramelia anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT leeseongki anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT occhipintirossana anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT kongqingzhong anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT shettyshashirekha anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT cohenmarkl anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT caugheybyron anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT schonbergerlawrenceb anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT applebybrians anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT caliignazio anovelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT bayazidrabeah novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT orruchristina novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT aslamrabail novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT cohenyvonne novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT silvarohweramelia novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT leeseongki novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT occhipintirossana novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT kongqingzhong novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT shettyshashirekha novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT cohenmarkl novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT caugheybyron novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT schonbergerlawrenceb novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT applebybrians novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques AT caliignazio novelsubtypeofsporadiccreutzfeldtjakobdiseasewithprnpcodon129mmgenotypeandprpplaques |