Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrPSc from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification
© 2023. The Author(s)..
Three retrospective lymphoreticular tissue studies (Appendix I, II, and III) aimed to estimate the UK prevalence of variant Creutzfeldt-Jakob disease (vCJD), following exposure of the population to the bovine spongiform encephalopathy (BSE) agent, in the late 1980s and 1990s. These studies evaluated the presence of abnormal prion protein aggregates, in archived formalin-fixed paraffin-embedded (FFPE) appendectomy samples, by immunohistochemical detection. Although there was concordance in the estimated prevalence of vCJD from these studies, the identification of positive specimens from pre- and post-BSE-exposure periods in Appendix III study has raised questions regarding the nature and origin of the detected abnormal prion protein. We applied a robust and novel approach in the extraction of disease-associated prion protein (PrPSc) present in frozen and FFPE samples of brain and appendix from a patient with pathologically confirmed vCJD. The extracted material was used to seed the highly sensitive protein misfolding cyclic amplification assay (hsPMCA) to investigate the in vitro and in vivo propagation properties of the extracted abnormal prion protein. We demonstrate that PrPSc can be successfully extracted from FFPE appendix tissue and propagated in vitro. Bioassay in wild-type and gene-targeted mouse models confirmed that the extracted and amplified product is infectious and retains strain properties consistent with vCJD. This provides a highly sensitive and reliable platform for subsequent analysis of the archived FFPE appendix tissue derived from the Appendix II and III surveys, to further evaluate the nature of the abnormal PrP detected in the positive samples.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:60 |
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| Enthalten in: |
Molecular neurobiology - 60(2023), 11 vom: 13. Nov., Seite 6275-6293 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Suleiman, Suzanne [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.09.2023 Date Revised 30.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s12035-023-03444-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Conservation of vCJD Strain Properties After Extraction and In Vitro Propagation of PrPSc from Archived Formalin-Fixed Brain and Appendix Tissues Using Highly Sensitive Protein Misfolding Cyclic Amplification |
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| 520 | |a Three retrospective lymphoreticular tissue studies (Appendix I, II, and III) aimed to estimate the UK prevalence of variant Creutzfeldt-Jakob disease (vCJD), following exposure of the population to the bovine spongiform encephalopathy (BSE) agent, in the late 1980s and 1990s. These studies evaluated the presence of abnormal prion protein aggregates, in archived formalin-fixed paraffin-embedded (FFPE) appendectomy samples, by immunohistochemical detection. Although there was concordance in the estimated prevalence of vCJD from these studies, the identification of positive specimens from pre- and post-BSE-exposure periods in Appendix III study has raised questions regarding the nature and origin of the detected abnormal prion protein. We applied a robust and novel approach in the extraction of disease-associated prion protein (PrPSc) present in frozen and FFPE samples of brain and appendix from a patient with pathologically confirmed vCJD. The extracted material was used to seed the highly sensitive protein misfolding cyclic amplification assay (hsPMCA) to investigate the in vitro and in vivo propagation properties of the extracted abnormal prion protein. We demonstrate that PrPSc can be successfully extracted from FFPE appendix tissue and propagated in vitro. Bioassay in wild-type and gene-targeted mouse models confirmed that the extracted and amplified product is infectious and retains strain properties consistent with vCJD. This provides a highly sensitive and reliable platform for subsequent analysis of the archived FFPE appendix tissue derived from the Appendix II and III surveys, to further evaluate the nature of the abnormal PrP detected in the positive samples | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Creutzfeldt-Jakob disease (CJD), Bovine spongiform encephalopathy (BSE) | |
| 650 | 4 | |a Neurodegenerative disorders | |
| 650 | 4 | |a Prion | |
| 650 | 4 | |a Protein misfolding | |
| 650 | 4 | |a Protein misfolding cyclic amplification assay (PMCA) | |
| 650 | 7 | |a Prion Proteins |2 NLM | |
| 650 | 7 | |a Prions |2 NLM | |
| 700 | 1 | |a McGuire, Lynne I |e verfasserin |4 aut | |
| 700 | 1 | |a Chong, Angela |e verfasserin |4 aut | |
| 700 | 1 | |a Ritchie, Diane L |e verfasserin |4 aut | |
| 700 | 1 | |a Boyle, Aileen |e verfasserin |4 aut | |
| 700 | 1 | |a McManus, Lee |e verfasserin |4 aut | |
| 700 | 1 | |a Brydon, Fraser |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Colin |e verfasserin |4 aut | |
| 700 | 1 | |a Knight, Richard |e verfasserin |4 aut | |
| 700 | 1 | |a Green, Alison |e verfasserin |4 aut | |
| 700 | 1 | |a Diack, Abigail B |e verfasserin |4 aut | |
| 700 | 1 | |a Barria, Marcelo A |e verfasserin |4 aut | |
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