Fig. 2

Transcriptomic and co-expression network analysis reveal impaired microglial response to AD-related pathology. a Transcriptome-wide response comparison of STD and TWD mice to A+ and A+T+ background. Plots show Z-statistics derived from DE analysis for A+Tw/STD vs. AwTw/STD (x-axis) and A+Tw/TWD vs. AwTw/TWD (y-axis) (left) and A+T+/STD vs. AwTw/STD (x-axis) and A+T+/TWD vs. AwTw/TWD (y-axis) (right). Points (genes) showing concordant response in STD and TWD cases are indicated in red, and discordant response for TWD as compared to STD, in blue. Genome-wide correlations of Z statistics and the corresponding correlation values are indicated on the top of each panel. b Enrichment analysis of genes showing discordant response to A+ or A+T+ background in TWD mice as compared to STD mice (blue dots in a). Enrichment ratio = number of observed divided by the number of expected genes. c WGCNA modules significantly associated to genotype in either STD or TWD mice. The color and value in the box represent correlation coefficient value. The value in parentheses represents corresponding correlation p-value. d Enrichment analysis for WGCNA module genes. Color indicates FDR value and size enrichment ratio. e Box plots representing eigengene values for modules positively associated with genotype. Points represent eigengene values for each mouse in that group. Box plots show the median, 25th and 75th percentiles, error bars show 1.5 interquartile ranges. f Z-score value heatmap of DE genes for STD vs. TWD mice with FDR < 0.005 and enriched transcription factors (TFs) with FDR < 0.05. n = 4–6 mice/group. AwTw = wild-type, AwT+ = Tau P301L, A+Tw = APPswe/PS1dE9, A+T+ = APPswe/PS1dE9 x Tau P301L