IntroductionMicroglia are tissue macrophages of the central nervous system that monitor brain homeostasis and react upon neuronal damage and stress. Aging and neurodegeneration induce a hypersensitive, pro-inflammatory phenotype, referred to as primed microglia. To determine the gene expression signature of priming, the transcriptomes of microglia in aging, Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS) mouse models were compared using Weighted Gene Co-expression Network Analysis (WGCNA).ResultsA highly consistent consensus transcriptional profile of up-regulated genes was identified, which prominently differed from the acute inflammatory gene network induced by lipopolysaccharide (LPS). Where the acute inflammatory network was significantly enriched for NF-κB signaling, the primed microglia profile contained key features related to phagosome, lysosome, antigen presentation, and AD signaling. In addition, specific signatures for aging, AD, and ALS were identified.ConclusionMicroglia priming induces a highly conserved transcriptional signature with aging- and disease-specific aspects.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0203-5) contains supplementary material, which is available to authorized users.

Disease Research (CNDR). Written informed consent was obtained from all subjects. The cases used in this study are summarized in Supplemental Table 3. RNA-seq data. All original RNA-seq data were previously deposited in the NCBI's Gene Expression Omnibus database (GEO GSE101689).

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