Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau

Alzheimer’s disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Usi...

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Autores principales: Kang, Silvia S., Ebbert, Mark T.W., Baker, Kelsey E., Cook, Casey, Wang, Xuewei, Sens, Jonathon P., Kocher, Jeanne-Pierre, Petrucelli, Leonard, Fryer, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122978/
https://www.ncbi.nlm.nih.gov/pubmed/30082275
http://dx.doi.org/10.1084/jem.20180653
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author Kang, Silvia S.
Ebbert, Mark T.W.
Baker, Kelsey E.
Cook, Casey
Wang, Xuewei
Sens, Jonathon P.
Kocher, Jeanne-Pierre
Petrucelli, Leonard
Fryer, John D.
author_facet Kang, Silvia S.
Ebbert, Mark T.W.
Baker, Kelsey E.
Cook, Casey
Wang, Xuewei
Sens, Jonathon P.
Kocher, Jeanne-Pierre
Petrucelli, Leonard
Fryer, John D.
author_sort Kang, Silvia S.
collection PubMed
description Alzheimer’s disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Using this approach in models of amyloidosis, tauopathy, and aging, we revealed a common set of alterations and identified a central APOE-driven network that converged on CCL3 and CCL4 across all conditions. Notably, aged females demonstrated a significant exacerbation of many of these shared transcripts in this APOE network, revealing a potential mechanism for increased AD susceptibility in females. This study has broad implications for microglial transcriptomic approaches and provides new insights into microglial pathways associated with different pathological aspects of aging and AD.
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spelling pubmed-61229782019-03-03 Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau Kang, Silvia S. Ebbert, Mark T.W. Baker, Kelsey E. Cook, Casey Wang, Xuewei Sens, Jonathon P. Kocher, Jeanne-Pierre Petrucelli, Leonard Fryer, John D. J Exp Med Research Articles Alzheimer’s disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. We show that a RiboTag translational profiling approach can bypass biases due to cellular enrichment/cell sorting. Using this approach in models of amyloidosis, tauopathy, and aging, we revealed a common set of alterations and identified a central APOE-driven network that converged on CCL3 and CCL4 across all conditions. Notably, aged females demonstrated a significant exacerbation of many of these shared transcripts in this APOE network, revealing a potential mechanism for increased AD susceptibility in females. This study has broad implications for microglial transcriptomic approaches and provides new insights into microglial pathways associated with different pathological aspects of aging and AD. Rockefeller University Press 2018-09-03 /pmc/articles/PMC6122978/ /pubmed/30082275 http://dx.doi.org/10.1084/jem.20180653 Text en © 2018 Kang et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Kang, Silvia S.
Ebbert, Mark T.W.
Baker, Kelsey E.
Cook, Casey
Wang, Xuewei
Sens, Jonathon P.
Kocher, Jeanne-Pierre
Petrucelli, Leonard
Fryer, John D.
Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
title Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
title_full Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
title_fullStr Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
title_full_unstemmed Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
title_short Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
title_sort microglial translational profiling reveals a convergent apoe pathway from aging, amyloid, and tau
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122978/
https://www.ncbi.nlm.nih.gov/pubmed/30082275
http://dx.doi.org/10.1084/jem.20180653
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