Fig. 4

Differential expression analysis in cognitively normal older adults and Plcg2- inactivated mouse model identified inflammation-related pathways. The volcano plot shows significant DEGs (fold change>1.5, FDR-corrected p<0.05) in cognitively normal older adults (CN) with lower (bottom 25%; n=50; low) versus higher (top 25%; n=50; high) expression of PLCG2 (a). Gene-set enrichment analysis was performed on the DEGs (fold change>1.5, FDR-corrected p<0.05) to identify GO terms, including inflammatory response (b). The volcano plot shows significant DEGs derived from the NanoString analysis of the brains of Plcg2 inactivation (PLCG2 ^inact, n=3) and WT (n=3) mice (1-month male) (c). Immunostaining of microglial markers with IBA1 (green) and P2RY12 (red) and quantification of percent area in brain sections of 1-month-old male WT and PLCG2 ^inact demonstrate unchanged microglial morphology and area coverage (d). GO gene ontology, BP biological process, DEGs differentially expressed genes, FDR false discovery rate