Abstract
Abstract Alzheimer’s disease (AD) is a neurodegenerative disease characterized pathologically by amyloidosis, tauopathy, and activation of microglia, the resident innate immune cells of the brain. Using a translational RiboTag profiling approach, we found that cellular isolation methods (enzymatic digestion, myelin removal, and CD45/CD11b sorting) altered the microglial transcriptome due to microglia activation and potential cellular contamination from sorting. Additionally, lipopolysaccharide-induced systemic inflammation generated completely different “top hits” from microglial RiboTag vs cellular isolation RNAseq datasets, likely due to microglial activation during the isolation process. RiboTag profiling of mouse models of AD revealed many significantly altered microglial transcripts that were shared between amyloidosis and tauopathy models, forming a network containing apolipoprotein E (APOE), CCL3, and CCL4. Inflammation and neutrophil chemotaxis pathways were also significantly enriched amongst the shared transcripts. This study has broad implications for microglial transcriptomic approaches and provides insights on microglial pathways associated with different pathological aspects of AD.
Published Version
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