Fig. 8.

Trem2^R47H initially suppresses then enhances neuroinflammation with age/disease progression. a Volcano plot of DEGs, displaying fold change of gene expression (log₂ scale) and P values (− log₁₀ scale) at 4- (upper panel) and 12-months old (lower panel) between Trem2^R47H vs wild-type, 5xFAD vs wild-type, and 5xFAD/Trem2^R47H vs 5xFAD. b Heatmap of selected DEGs in 5xFAD/Trem2^R47H vs 5xFAD at 12-months old, showing the list of uniquely upregulated genes only in 5xFAD/Trem2^R47H highlighting multiple interferon-related genes (FDR < 0.1). In second row of heatmap, pink boxes denote females while blue boxes denote males. c Gene network map shows connections of DEGs between 12-month-old 5xFAD/Trem2^R47H and 5xFAD mice. d Heatmap generated from selected DEGs in the inflammation (Darkgrey) module. e Eigengene of the Darkgrey module plotted as bar graphs for WT, Trem2^R47H, 5xFAD and 5xFAD/Trem2^R47H at 4- and 12-month timepoints. f Gene ontology of the Darkgrey module shows increased neutrophil responses and pathways. g, h Volcano plot of DEGs, displaying fold change of gene expression (log₂ scale) and P values (− log₁₀ scale) of (g) female and (h) male 5xFAD/Trem2^R47H vs 5xFAD at 12-months old. i Heatmap generated from DEGs between 5xFAD/Trem2^R47H vs 5xFAD vs females at 12 months. i Gene oncology of the DEGs between 5xFAD/Trem2^R47H vs 5xFAD females at 12 months. j Bioplanet pathways associated with the DEGs between 5xFAD/Trem2^R47H vs 5xFAD females at 12 months. Eigengene bar plots—n = 10–15. Data are represented as mean ± SEM. Two-way ANOVA followed by Tukey’s post hoc tests to examine biologically relevant interactions. Statistical significance is denoted by *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001