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

doi:10.1084/jem.20180653

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 journal › Article › peer-review

172 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 language	English
Pages (from-to)	2235-2245
Number of pages	11
Journal	Journal of Experimental Medicine
Volume	215
Issue number	9
DOIs	https://doi.org/10.1084/jem.20180653
State	Published - 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

Funding

This work was supported by grants from Mayo Foundation, GHR Foundation, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Gerstner Family Career Development Award, Ed and Ethel Moore Alzheimer’s Disease Research Program of Florida Department of Health (grant 6AZ06 to J.D. Fryer), and National Institutes of Health grants NS094137, AG047327, and AG049992 (to J.D. Fryer); MH103632 (to S.S. Kang); AG057997 and AG016574 (J.D. Fryer and S.S. Kang); NS100693, NS097273, NS084974, and NS100693 (L. Petrucelli). The authors declare no competing financial interests.

Funders	Funder number
Ed and Ethel Moore Alzheimer’s Disease Research Program of Florida Department of Health	6AZ06
GHR Foundation
National Institutes of Health (NIH)	NS097273, AG049992, AG016574, NS084974, MH103632, NS100693, AG047327, AG057997
National Institutes of Health (NIH)
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS094137
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
Mayo Clinic Rochester
Mayo Foundation for Medical Education and Research

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1084/jem.20180653

Cite this

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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.",

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AU - Kang, Silvia S.

AU - Ebbert, Mark T.W.

AU - Baker, Kelsey E.

AU - Cook, Casey

AU - Wang, Xuewei

AU - Sens, Jonathon P.

AU - Kocher, Jeanne Pierre

AU - Petrucelli, Leonard

AU - Fryer, John D.

N1 - 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

PY - 2018

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

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