Insights into TREM2 biology by network analysis of human brain gene expression data

详细信息    查看全文

• 作者：Paola Forabosco ; Adaikalavan Ramasamy ; Daniah Trabzuni ; Robert Walker ; Colin Smith ; Jose Bras ; Adam P. Levine ; John Hardy ; Jennifer M. Pocock ; Rita Guerreiro ; Michael E. Weale ; Mina Ryten
• 关键词：TREM2 ; Weighted gene co-expression network analysis ; Alzheimer's disease ; Post-mortem human brain ; Microglia ; Immune system
• 刊名：Neurobiology of Aging
• 出版年：2013
• 出版时间：December, 2013
• 年：2013
• 卷：34
• 期：12
• 页码：2699-2714
• 全文大小：4564 K

文摘

Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease. Here we use microarray-based expression data generated from 101 neuropathologically normal individuals and covering 10 brain regions, including the hippocampus, to understand TREM2 biology in human brain. Using network analysis, we detect a highly preserved TREM2-containing module in human brain, show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5 brain regions, including the hippocampus, suggesting that it can drive module function. Using enrichment analysis we show significant overrepresentation of genes implicated in the adaptive and innate immune system. Inspection of genes with the highest connectivity to TREM2 suggests that it plays a key role in mediating changes in the microglial cytoskeleton necessary not only for phagocytosis, but also migration. Most importantly, we show that the TREM2-containing module is significantly enriched for genes genetically implicated in Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia and that among the genes identified are possible new disease-relevant genes.