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Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models
Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences. Here, we performed an in-depth and time-resolved proteomic characterization of microglia in t...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279888/ https://www.ncbi.nlm.nih.gov/pubmed/32510331 http://dx.doi.org/10.7554/eLife.54083 |
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author | Sebastian Monasor, Laura Müller, Stephan A Colombo, Alessio Vittorio Tanrioever, Gaye König, Jasmin Roth, Stefan Liesz, Arthur Berghofer, Anna Piechotta, Anke Prestel, Matthias Saito, Takashi Saido, Takaomi C Herms, Jochen Willem, Michael Haass, Christian Lichtenthaler, Stefan F Tahirovic, Sabina |
author_facet | Sebastian Monasor, Laura Müller, Stephan A Colombo, Alessio Vittorio Tanrioever, Gaye König, Jasmin Roth, Stefan Liesz, Arthur Berghofer, Anna Piechotta, Anke Prestel, Matthias Saito, Takashi Saido, Takaomi C Herms, Jochen Willem, Michael Haass, Christian Lichtenthaler, Stefan F Tahirovic, Sabina |
author_sort | Sebastian Monasor, Laura |
collection | PubMed |
description | Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences. Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid β (Aβ) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial Aβ Response Proteins (MARPs) that reflect heterogeneity of microglial alterations during early, middle and advanced stages of Aβ deposition and occur earlier in the APPPS1 mice. Strikingly, the kinetic differences in proteomic profiles correlated with the presence of fibrillar Aβ, rather than dystrophic neurites, suggesting that fibrillar Aβ may trigger the AD-associated microglial phenotype and the observed functional decline. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy. |
format | Online Article Text |
id | pubmed-7279888 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-72798882020-06-10 Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models Sebastian Monasor, Laura Müller, Stephan A Colombo, Alessio Vittorio Tanrioever, Gaye König, Jasmin Roth, Stefan Liesz, Arthur Berghofer, Anna Piechotta, Anke Prestel, Matthias Saito, Takashi Saido, Takaomi C Herms, Jochen Willem, Michael Haass, Christian Lichtenthaler, Stefan F Tahirovic, Sabina eLife Neuroscience Microglial dysfunction is a key pathological feature of Alzheimer's disease (AD), but little is known about proteome-wide changes in microglia during the course of AD and their functional consequences. Here, we performed an in-depth and time-resolved proteomic characterization of microglia in two mouse models of amyloid β (Aβ) pathology, the overexpression APPPS1 and the knock-in APP-NL-G-F (APP-KI) model. We identified a large panel of Microglial Aβ Response Proteins (MARPs) that reflect heterogeneity of microglial alterations during early, middle and advanced stages of Aβ deposition and occur earlier in the APPPS1 mice. Strikingly, the kinetic differences in proteomic profiles correlated with the presence of fibrillar Aβ, rather than dystrophic neurites, suggesting that fibrillar Aβ may trigger the AD-associated microglial phenotype and the observed functional decline. The identified microglial proteomic fingerprints of AD provide a valuable resource for functional studies of novel molecular targets and potential biomarkers for monitoring AD progression or therapeutic efficacy. eLife Sciences Publications, Ltd 2020-06-08 /pmc/articles/PMC7279888/ /pubmed/32510331 http://dx.doi.org/10.7554/eLife.54083 Text en © 2020, Sebastian Monasor et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Sebastian Monasor, Laura Müller, Stephan A Colombo, Alessio Vittorio Tanrioever, Gaye König, Jasmin Roth, Stefan Liesz, Arthur Berghofer, Anna Piechotta, Anke Prestel, Matthias Saito, Takashi Saido, Takaomi C Herms, Jochen Willem, Michael Haass, Christian Lichtenthaler, Stefan F Tahirovic, Sabina Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models |
title | Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models |
title_full | Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models |
title_fullStr | Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models |
title_full_unstemmed | Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models |
title_short | Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models |
title_sort | fibrillar aβ triggers microglial proteome alterations and dysfunction in alzheimer mouse models |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279888/ https://www.ncbi.nlm.nih.gov/pubmed/32510331 http://dx.doi.org/10.7554/eLife.54083 |
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