Fig. 7: Trem2 deficiency and APOE isoform affect microglia response to Aβ.

a–c Scatter plots, bar plots, and feature plots showing the differentially expressed genes in microglia from WT and Trem2^ko mice injected with AβE4 or AβE3 complexes for cluster 2 (a), cluster 3 (b), and cluster 4 (c). Differentially expressend genes at p < 0.01 are colored in each cluster color. The adjusted P value was performed using Bonferroni correction. Genes labeled with black color indicate commonly up- or down-regulated genes in AβE3 or AβE4 injected mice. Genes labeled with red indicate uniquely upregulated genes in WT-AβE3 or WT-AβE4 and genes labeled blue is uniquely upregulated genes in Trem2^ko-AβE3 or Trem2^ko-AβE4. n = 2 mice per group (WT-AβE3, WT-AβE4, Trem2^ko-AβE3, and Trem2^ko-AβE4). d, e Microglia established from WT and Trem2^ko mice were treated with and 555-labeled Aβ for 1 h. d Representative images of microglia from WT and Trem2^ko mice incubated with AβE4 or AβE3 labeled with IBA1 in green and 555-labeled Aβ in red. e Bar plot showing the average percentage of Aβ-containing microglia for each group (WT-AβE3 purple, WT-AβE4, green, Trem2^ko-AβE3 light purple, and Trem2^ko-AβE4 light green). n = 3 independent cultures at least in triplicate. Analysis by one-way ANOVA followed by Tukey’s multiple comparison test. WT-AβE3 vs. WT-AβE4, p = 0.0008; Trem2^ko-AβE3 vs. Trem2^ko-AβE4, p < 0.0001; WT-AβE4 vs. Trem2^ko-AβE4, p = 0.0485. Violin plots represent kernel densities for each dataset showing median (middle line) and 75% (top) and 25% percentile (bottom). *p < 0.05; ***p < 0.001.