TY - JOUR
T1 - Microglial translational profiling reveals a convergent APOE pathway from aging, amyloid, and tau
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
Y1 - 2018
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85055867324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055867324&partnerID=8YFLogxK
U2 - 10.1084/jem.20180653
DO - 10.1084/jem.20180653
M3 - Article
C2 - 30082275
AN - SCOPUS:85055867324
SN - 0022-1007
VL - 215
SP - 2235
EP - 2245
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 9
ER -