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

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

Research output: Contribution to journalArticle

31 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 (US)
Pages (from-to)2235-2245
Number of pages11
JournalJournal of Experimental Medicine
Volume215
Issue number9
DOIs
StatePublished - Jan 1 2018

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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