Fig. 6

Reversal of transcriptomic profiles enriched in cerebrovascular and mitochondrial functions in bevacizumab-treated 5×FAD mice. a Experimental design and the workflow of the RNA-seq analysis. b Principal component analysis (PCA) plot of the RNA-seq results (n = 3 pools per group, 2–3 animals of the same sex per pool). c Volcano plots of the DEGs of the female groups, with horizontal lines at −log10 (P value) = −log10 (0.05) and vertical lines at log2 (fold change, FC) = log2 (1.5). d Volcano plots of the DEGs of the male groups. e Venn diagram depicting limited overlaps of the DEGs of the female groups. f Venn diagram depicting limited overlaps of the DEGs of the male groups. g Heatmaps of the DEGs affected by bevacizumab treatment in female 5×FAD mice. Twenty-three DEGs were upregulated in 5×FAD mice compared with wild-type mice but downregulated after bevacizumab treatment. Thirty-two DEGs were downregulated in 5×FAD mice but upregulated after bevacizumab treatment. h Heatmaps of the DEGs affected by bevacizumab treatment in male 5×FAD mice. Five DEGs were upregulated in 5×FAD mice but downregulated after bevacizumab treatment. Nineteen DEGs were downregulated in 5×FAD mice but upregulated after bevacizumab treatment. i, j Cell-type enrichment analysis of DEGs in the (i) female groups and (j) male groups. k, l Quantitative PCR validation of DEGs identified from 5×FAD versus wild-type groups, which were reversed by bevacizumab treatment in the (k) female (n = 6–8 mice per group) and (l) male (n = 7–9 mice per group) groups. All data are presented as the mean ± SEM and were analyzed by one-way ANOVA followed by Fisher’s LSD test. m KEGG pathway analysis based on GSEA was performed for RNA-seq data of the female and male 5×FAD mice. WT (Veh): wild-type littermates receiving sham treatment, AD (Veh): 5×FAD mice receiving sham treatment, AD (Bev): 5×FAD mice receiving bevacizumab treatment