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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
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.
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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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