Fig. 3: Tau and amyloid pathology trigger a core set of gene expression changes in astrocytes.

A A heat map of genes induced (red) and repressed (blue) in both MAPT^P301S and APP/PS1 mice. B Genes induced in astrocytes in both MAPT^P301S and APP/PS1 mice (p_adj < 0.05 in both sample sets) were subjected to enrichment analysis against the indicated gene sets. *3.3E−07, 4.6E−12, 1.9E−34, 6.4E−07, 2.0E−05, 3.1E−13, 2.4E−19 (two-sided Fisher’s exact test). Fold enrichment and 95% CI shown. C (Left) Enrichment analysis of genes induced in human AD astrocytes⁷ for which a 1:1 ortholog exists (and >10 FPKM cut-off) for genes induced in MAPT^P301S astrocytes (Fig. 1C), APP/PS1 astrocytes (Fig. 1H), or those induced in both models (A). Fold enrichment and 95% CI shown, *p = 9.4E−05, 4.1E−11, 4.0E−08 (two-sided Fisher’s exact test). (Right) For genes induced in human AD astrocytes⁷ for which a 1:1 ortholog exists and that are expressed >10 FPKM in MAPT^P301S and APP/PS1 astrocytes, the Log(2) fold change in each gene is shown for both models (y-axis: MAPT^P301S vs. WT; x-axis: APP/PS1 vs. WT). For each gene, in indication of whether it is significantly (p < 0.05) induced in either, both, or neither models is indicated. Ontological analysis of genes induced (D) or repressed (E) in astrocytes in both MAPT^P301S and APP/PS1 mice. For KEGG pathway analysis, disease pathways were omitted (to enable a focus on biological pathways) and the number of genes required was ≥5. For KEGG and GO ontology analysis the top ten pathways are shown, unless fewer than ten achieved an adjusted p value cut-off of 0.05.