Translational profiling of microglia reveals a shared apoE pathway common to aging, amyloid, and tau pathology
John D. Fryer1,3*, Silvia S. Kang1, Kelsey E. Baker1, Casey Cook1, Xuewei Wang2, Jonathon Sens1,3, Jeanne-Pierre Kocher2, Mark T.W. Ebbert1
1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA;
2Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA;
3Neurobiology of Disease Graduate Program, Mayo Clinic Graduate School of Biomedical Sciences, Jacksonville, FL 32224, USA
Alzheimer's disease (AD) is an age-associated neurodegenerative disease characterized by amyloidosis, tauopathy, and activation of microglia, the brain resident innate immune cells. Using RiboTag microglial translational profiling in models of amyloidosis, tauopathy, or aging, we found a striking overlap among these conditions including a previously unreported robust induction of Ccl3 and Ccl4, in addition to Apoe, Cst7, Lgals3, and Itgax. ApoE was among the 0.2% of all microglial transcripts based on absolute abundance and was a critical driver of a pathway that converged on the chemokines CCL3 and CCL4. Interestingly, aged females were significantly worse than aged males for this shared signature. 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.