Fig. 7

Trem2 H157Y downregulates genes related to neuroinflammation pathway in 5xFAD mice. Cortical bulk RNA sequencing was conducted with mice at 8.5 months of age (4–5 mice/sex/genotype). A. In the comparison of Hom and WT mice, upregulated or downregulated differentially expressed genes (DEG, Hom vs. WT, |Fold change|> 1.2; FDR< 0.05) were identified and indicated in red or blue in the volcano plot. B. Hierarchical clustering for DEG expression (Hom vs WT) is shown across each sample. DEGs involved in the top 10 pathways (C) are shown in blue. C. Top 10 DEG related pathways were identified through Ingenuity Pathway Analysis (IPA). Red dashed line indicates the FDR threshold, 0.05. D. Weighted gene co-expression network analysis (WGCNA) identified a unique magenta module which is downregulated in Hom and correlated with amyloid pathological readouts. E. Magenta module eigengenes (ME) were compared between WT and Hom mice. Data are presented as Mean ± SEM. Wilcoxon rank sum test was used. F. Top 10 gene ontology (GO) terms (FDR < 0.05) are shown for the magenta module. G. Network plot of genes involved in the top 10 GO terms was generated through Cytoscape. H. TNF-α in the TBS lysate was quantified and normalized to WT mice for each genotype. N = 19–24 mice per genotype at 8.5 months of age, mixed sex. Data are presented as Mean ± SEM. Kruskal–Wallis tests with uncorrected Dun’s multiple comparisons were used. * p < 0.05. **p < 0.01