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APOE ε2 is associated with increased tau pathology in primary tauopathy
Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease mainly by modulating amyloid-β pathology. APOE ε4 is also shown to exacerbate neurodegeneration and neuroinflammation in a tau transgenic mouse model. To further evaluate the association of APOE...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197187/ https://www.ncbi.nlm.nih.gov/pubmed/30348994 http://dx.doi.org/10.1038/s41467-018-06783-0 |
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author | Zhao, Na Liu, Chia-Chen Van Ingelgom, Alexandra J. Linares, Cynthia Kurti, Aishe Knight, Joshua A. Heckman, Michael G. Diehl, Nancy N. Shinohara, Mitsuru Martens, Yuka A. Attrebi, Olivia N. Petrucelli, Leonard Fryer, John D. Wszolek, Zbigniew K. Graff-Radford, Neill R. Caselli, Richard J. Sanchez-Contreras, Monica Y. Rademakers, Rosa Murray, Melissa E. Koga, Shunsuke Dickson, Dennis W. Ross, Owen A. Bu, Guojun |
author_facet | Zhao, Na Liu, Chia-Chen Van Ingelgom, Alexandra J. Linares, Cynthia Kurti, Aishe Knight, Joshua A. Heckman, Michael G. Diehl, Nancy N. Shinohara, Mitsuru Martens, Yuka A. Attrebi, Olivia N. Petrucelli, Leonard Fryer, John D. Wszolek, Zbigniew K. Graff-Radford, Neill R. Caselli, Richard J. Sanchez-Contreras, Monica Y. Rademakers, Rosa Murray, Melissa E. Koga, Shunsuke Dickson, Dennis W. Ross, Owen A. Bu, Guojun |
author_sort | Zhao, Na |
collection | PubMed |
description | Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease mainly by modulating amyloid-β pathology. APOE ε4 is also shown to exacerbate neurodegeneration and neuroinflammation in a tau transgenic mouse model. To further evaluate the association of APOE genotype with the presence and severity of tau pathology, we express human tau via an adeno-associated virus gene delivery approach in human APOE targeted replacement mice. We find increased hyperphosphorylated tau species, tau aggregates, and behavioral abnormalities in mice expressing APOE ε2/ε2. We also show that in humans, the APOE ε2 allele is associated with increased tau pathology in the brains of progressive supranuclear palsy (PSP) cases. Finally, we identify an association between the APOE ε2/ε2 genotype and risk of tauopathies using two series of pathologically-confirmed cases of PSP and corticobasal degeneration. Our data together suggest APOE ε2 status may influence the risk and progression of tauopathy. |
format | Online Article Text |
id | pubmed-6197187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-61971872018-10-23 APOE ε2 is associated with increased tau pathology in primary tauopathy Zhao, Na Liu, Chia-Chen Van Ingelgom, Alexandra J. Linares, Cynthia Kurti, Aishe Knight, Joshua A. Heckman, Michael G. Diehl, Nancy N. Shinohara, Mitsuru Martens, Yuka A. Attrebi, Olivia N. Petrucelli, Leonard Fryer, John D. Wszolek, Zbigniew K. Graff-Radford, Neill R. Caselli, Richard J. Sanchez-Contreras, Monica Y. Rademakers, Rosa Murray, Melissa E. Koga, Shunsuke Dickson, Dennis W. Ross, Owen A. Bu, Guojun Nat Commun Article Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease mainly by modulating amyloid-β pathology. APOE ε4 is also shown to exacerbate neurodegeneration and neuroinflammation in a tau transgenic mouse model. To further evaluate the association of APOE genotype with the presence and severity of tau pathology, we express human tau via an adeno-associated virus gene delivery approach in human APOE targeted replacement mice. We find increased hyperphosphorylated tau species, tau aggregates, and behavioral abnormalities in mice expressing APOE ε2/ε2. We also show that in humans, the APOE ε2 allele is associated with increased tau pathology in the brains of progressive supranuclear palsy (PSP) cases. Finally, we identify an association between the APOE ε2/ε2 genotype and risk of tauopathies using two series of pathologically-confirmed cases of PSP and corticobasal degeneration. Our data together suggest APOE ε2 status may influence the risk and progression of tauopathy. Nature Publishing Group UK 2018-10-22 /pmc/articles/PMC6197187/ /pubmed/30348994 http://dx.doi.org/10.1038/s41467-018-06783-0 Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Zhao, Na Liu, Chia-Chen Van Ingelgom, Alexandra J. Linares, Cynthia Kurti, Aishe Knight, Joshua A. Heckman, Michael G. Diehl, Nancy N. Shinohara, Mitsuru Martens, Yuka A. Attrebi, Olivia N. Petrucelli, Leonard Fryer, John D. Wszolek, Zbigniew K. Graff-Radford, Neill R. Caselli, Richard J. Sanchez-Contreras, Monica Y. Rademakers, Rosa Murray, Melissa E. Koga, Shunsuke Dickson, Dennis W. Ross, Owen A. Bu, Guojun APOE ε2 is associated with increased tau pathology in primary tauopathy |
title | APOE ε2 is associated with increased tau pathology in primary tauopathy |
title_full | APOE ε2 is associated with increased tau pathology in primary tauopathy |
title_fullStr | APOE ε2 is associated with increased tau pathology in primary tauopathy |
title_full_unstemmed | APOE ε2 is associated with increased tau pathology in primary tauopathy |
title_short | APOE ε2 is associated with increased tau pathology in primary tauopathy |
title_sort | apoe ε2 is associated with increased tau pathology in primary tauopathy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197187/ https://www.ncbi.nlm.nih.gov/pubmed/30348994 http://dx.doi.org/10.1038/s41467-018-06783-0 |
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