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

Silvia S. Kang, Mark T.W. Ebbert, Kelsey E. Baker, Casey Cook, Xuewei Wang, Jonathon P. Sens, Jeanne Pierre Kocher, Leonard Petrucelli, John D. Fryer

Research output: Contribution to journalArticlepeer-review

137 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)2235-2245
Number of pages11
JournalJournal of Experimental Medicine
Volume215
Issue number9
DOIs
StatePublished - 2018

Bibliographical note

Publisher Copyright:
© 2018 Kang et al. 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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau'. Together they form a unique fingerprint.

Cite this