Fig. 1

Microglial activation markers in Grn ko and Trem2 ko are consistently changed on mRNA and protein level in mice and partially reflected in the mouse CSF proteome. (A-B) Volcano plots showing upregulated (red) and downregulated (blue) proteins in microglia isolated from mice with the following genotypic comparisons: (A)Grn ko / Wt and (B)Trem2 ko / Wt. Selected cut-off values: p-value < 0.05 (colored dots) and − 0.5 > Log2 FC > 0.50 (filled dots). The -log10 transformed p-value of each protein is plotted against its log2 fold change. (C-D) Log2 fold-changes (relative to age-matched Wt) of microglial expressed mRNAs and related proteins, show very similar transcriptomic and proteomic changes. mRNA signatures were generated in independent samples from Cd11b-positive microglia isolated from 5.5 months old Grn ko and Trem2 ko mice, respectively [11]. Crosses indicate missing values. (E-F) Comparing microglial proteome and transcriptome of Grn ko mice. (E) Significantly upregulated proteins (orange) versus significantly upregulated genes (pink). Overlap of 12 markers significantly upregulated on both protein and mRNA level (text box). (F) Significantly downregulated proteins (green) versus significantly downregulated genes (blue). Overlap of 14 markers significantly downregulated on both protein and mRNA level (text box). Selected cut-off values: p-value < 0.05. (G-H) Comparing upregulated (red) and downregulated (blue) proteins in mouse CSF with the following genotypic comparisons: (G)Grn ko / Wt and (H)Trem2 ko / Wt. Cathepsins, Lyz2, as well as Apoe and Lgals3 are marked in yellow, while Chi3l1 (a biomarker for neuroinflammation) is marked in purple. Other proteins of interest are marked in green. Selected cut-off values: p-value < 0.05 and − 0.5 > Log2 FC > 0.50. (I) Changes (relative to age-matched Wt) of Apoe, Ctsz, Ctsb, and Lyz2 are consistent in the proteome of isolated microglia and in the proteome of CSF sampled from the same mice. Statistical differences were calculated using Student’s t-test. * = p-value < 0.05, ** = p-value < 0.01, *** = p-value < 0.001; n.s. = non-significant. False discovery rate (FDR) was not considered for the presented visualizations. All presented proteomic data was obtained by LC-MS/MS. Proteomic data were generated from 12 months old mice using the following experimental groups: n (Grn ko microglia) = 4, n (Trem2 ko microglia) = 8, n (Wt microglia) = 7, n (Grn ko CSF) = 4, n (Trem2 ko CSF) = 4, n (Wt CSF) = 6