Cargando…
Variable tau accumulation in murine models with abnormal prion protein deposits
The conversion of cellular prion protein (PrP) into a misfolded isoform is central to the development of prion diseases. However, the heterogeneous phenotypes observed in prion disease may be linked with the presence of other misfolded proteins in the brain. While hyperphosphorylated tau (p.tau) is...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381323/ https://www.ncbi.nlm.nih.gov/pubmed/29246602 http://dx.doi.org/10.1016/j.jns.2017.10.040 |
_version_ | 1783396479996526592 |
---|---|
author | Piccardo, Pedro King, Declan Brown, Deborah Barron, Rona M. |
author_facet | Piccardo, Pedro King, Declan Brown, Deborah Barron, Rona M. |
author_sort | Piccardo, Pedro |
collection | PubMed |
description | The conversion of cellular prion protein (PrP) into a misfolded isoform is central to the development of prion diseases. However, the heterogeneous phenotypes observed in prion disease may be linked with the presence of other misfolded proteins in the brain. While hyperphosphorylated tau (p.tau) is characteristic of Alzheimer's disease (AD), p.tau is also observed in human prion diseases. To explore this association in the absence of potential effects due to aging, drug treatment, agonal stage and postmortem delay we analyzed p.tau and PrP immunopositivity in mouse models. Analyses were performed on mice inoculated with prion agents, and mice with PrP amyloid in the absence of prion disease. We observed that p.tau was consistently present in animals with prion infectivity (models that transmit disease upon serial passage). In contrast, p.tau was very rarely observed or absent in mice with PrP amyloid plaques in the absence of prion replication. These data indicate that the formation of p.tau is not linked to deposition of misfolded PrP, but suggest that the interaction between replication of infectivity and host factors regulate the formation of p.tau and may contribute to the heterogeneous phenotype of prion diseases. |
format | Online Article Text |
id | pubmed-6381323 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-63813232019-02-28 Variable tau accumulation in murine models with abnormal prion protein deposits Piccardo, Pedro King, Declan Brown, Deborah Barron, Rona M. J Neurol Sci Article The conversion of cellular prion protein (PrP) into a misfolded isoform is central to the development of prion diseases. However, the heterogeneous phenotypes observed in prion disease may be linked with the presence of other misfolded proteins in the brain. While hyperphosphorylated tau (p.tau) is characteristic of Alzheimer's disease (AD), p.tau is also observed in human prion diseases. To explore this association in the absence of potential effects due to aging, drug treatment, agonal stage and postmortem delay we analyzed p.tau and PrP immunopositivity in mouse models. Analyses were performed on mice inoculated with prion agents, and mice with PrP amyloid in the absence of prion disease. We observed that p.tau was consistently present in animals with prion infectivity (models that transmit disease upon serial passage). In contrast, p.tau was very rarely observed or absent in mice with PrP amyloid plaques in the absence of prion replication. These data indicate that the formation of p.tau is not linked to deposition of misfolded PrP, but suggest that the interaction between replication of infectivity and host factors regulate the formation of p.tau and may contribute to the heterogeneous phenotype of prion diseases. Elsevier 2017-12-15 /pmc/articles/PMC6381323/ /pubmed/29246602 http://dx.doi.org/10.1016/j.jns.2017.10.040 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Piccardo, Pedro King, Declan Brown, Deborah Barron, Rona M. Variable tau accumulation in murine models with abnormal prion protein deposits |
title | Variable tau accumulation in murine models with abnormal prion protein deposits |
title_full | Variable tau accumulation in murine models with abnormal prion protein deposits |
title_fullStr | Variable tau accumulation in murine models with abnormal prion protein deposits |
title_full_unstemmed | Variable tau accumulation in murine models with abnormal prion protein deposits |
title_short | Variable tau accumulation in murine models with abnormal prion protein deposits |
title_sort | variable tau accumulation in murine models with abnormal prion protein deposits |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381323/ https://www.ncbi.nlm.nih.gov/pubmed/29246602 http://dx.doi.org/10.1016/j.jns.2017.10.040 |
work_keys_str_mv | AT piccardopedro variabletauaccumulationinmurinemodelswithabnormalprionproteindeposits AT kingdeclan variabletauaccumulationinmurinemodelswithabnormalprionproteindeposits AT browndeborah variabletauaccumulationinmurinemodelswithabnormalprionproteindeposits AT barronronam variabletauaccumulationinmurinemodelswithabnormalprionproteindeposits |