Fig. 3
Multi-omics analysis of microglia from AppSAA KI/KI and control mice at 8 months of age. a FACS gating strategy for isolating microglia from whole brains of AppSAA homozygous mice (KI/KI), heterozygous mice (KI/+) and wild-type mice (+/+) at 8 months of age for transcriptomics, lipidomics, and metabolomics analysis. b Volcano plots showing log2 fold change of gene expression between AppSAA heterozygous (left) and homozygous (right) knock-in compared to WT; dark grey, fuchsia, and blue indicate DEGs (FDR <= 10%; see methods), DAM, and homeostatic genes, respectively. N = 6 mice per genotype. c Single sample activity scores for curated gene sets in AppSAA heterozygous, AppSAA homozygous, and 5xFAD. Intensities indicate log2 fold change of aggregated gene set score (row) per mouse (column) with respect to mean gene set score from matched WT mice. N = 5-6 mice per genotype. d Volcano plot showing log2 fold change of lipids between AppSAA homozygous mice compared to WT. FDR <= 10%; absolute fold change > 20%. N = 6 mice per genotype. e Heatmap of top 10 lipids significantly altered by genotype in isolated microglia; columns represent individual mice. Intensities indicate log2 fold change of lipids with respect to mean abundance in WT mice. N = 6 mice per genotype