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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1783352767185682432 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6122978 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kangsilvias microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau AT ebbertmarktw microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau AT bakerkelseye microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau AT cookcasey microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau AT wangxuewei microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau AT sensjonathonp microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau AT kocherjeannepierre microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau AT petrucellileonard microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau AT fryerjohnd microglialtranslationalprofilingrevealsaconvergentapoepathwayfromagingamyloidandtau |