Fig. 3

Overlapping proteomic changes observed in the CSF proteome of symptomatic GRN carriers and the secretome of GRN ko hiMGL. (A) Comparison of the CSF proteome of symptomatic heterozygous GRN mutation-carriers (FTD-GRN, n = 11) and healthy controls (CON, n = 12). Significantly upregulated proteins (red) versus significantly downregulated proteins (blue) are shown. 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. (B) Identification of microglial activity state-dependent proteins by comparing the significantly upregulated proteins in human CSF of FTD-GRN patients (orange) to the significantly upregulated proteins detected in the conditioned media of GRN ko hiMGL (pink). In the CSF of FTD-GRN patients, 88 proteins were significantly upregulated compared to healthy non-carriers. 26 (30%) of these proteins were also detected as significantly upregulated in the conditioned media of hiMGL lacking GRN compared to media of WT hiMGL (box). (C) Quantitative comparison of the 26 proteins detected as significantly upregulated in both, the human CSF (hCSF) of FTD-GRN patients (orange) and the media of GRN ko hiMGL (pink) presented as Log2 Fold Change in relation to respective control (CON and WT, respectively). Proteins of interest are marked in yellow and green. 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 were obtained by LC-MS/MS.