Distinct Signatures for Human Microglia in Alzheimer ' s Disease

This study identified 10 distinct microglia clusters from aged human brain. These included previously described homeostatic, senescent, and inflammatory microglia transcriptional phenotypes as well as additional clusters of transcriptional specification, which may give insight into AD pathogenesis, providing a platform for hypothesis generation. We describe the diversity of microglia clusters with endolysosomal gene signatures, one of which is enriched with nucleic acid recognition and interferon regulation genes. Inferred gene networks predict that individual clusters are driven by distinct transcription factors, lending further support for the functional diversity of clusters. Using trajectory inference analysis, we observed transitions in microglia phenotypes and predicted relationships that can be tested experimentally. AD cases were distinguished by the emergence of a subcluster expressing homeostatic genes that was characterized by altered transcription of genes involved in calcium activation, response to injury, and motility pathways. Among the nuclei meeting criteria for a microglia transcriptomic signature, an 'aging signature' was observed in all clusters in this study, consistent with our older age cohort. Inflammaging may not only confound interpretations of gene expression profiles attributable to AD but may also contribute to the disease mechanisms hypothesized to drive AD. Additional studies exploring differences between younger controls and early-onset ...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs