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

• DOI: 10.1084/jem.20180653
• Publication Date: 2018-08-06T14:45:14Z
• Authors: 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
• Keywords: Apolipoprotein E; Posttranslational modification; Amyloid (mycology); Profiling (computer programming)

Alzheimer's disease (AD) is an age-associated neurodegenerative 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 in models aging, we revealed common set alterations identified central APOE-driven network converged on CCL3 CCL4 across all conditions. Notably, aged females demonstrated significant exacerbation many these shared transcripts APOE network, revealing potential mechanism for increased AD susceptibility females. This study has broad implications microglial transcriptomic approaches provides new insights into pathways associated with different pathological aspects aging AD.