Fig. 4
Analysis of dysregulated proteins of 5xFAD brains and postmortem brains of AD patients. a Investigation of the overlap of DEPs in brains of 5xFAD mice and postmortem AD patients. Protein changes in cortical and hippocampal tissues of 8- and 5-month-old mice (DE.cortex.Age8; DE.hippo.Age5; DE.hippo.Age8) that contain Aβ aggregates (Fig. 1d) were compared with patient protein measurements. The amounts of DEPs are denoted analogously to Fig. 2a or have been abbreviated (C8, H5, H8). The human AD data were obtained from Drummond 2022 (D22, [43]), Johnson 2020 (J20, [41]), and Johnson 2022 (J22, [42]). The total numbers of DEPs in each dataset are indicated in brackets. In DE.cortex.Age8 and DE.hippo.Age5, the proteins present in all four data sets are depicted with gene names. b Correlation analyses of DEPs from cortical tissues of 8-month-old mice (DE.cortex.Age8) and DEPs from hippocampal tissues of 5- (DE.hippo.Age5) and 8-month-old mice (DE.hippo.Age8) with human AD patient data from Drummond 2022, Johnson 2020 and Johnson 2022 (as indicated in panel a) were performed. The degree of correlation was assessed by Spearman correlation coefficients (rS) and corresponding FDR-adjusted p-values (*, p < 0.05; **, p < 0.01; ***, p < 0.001). Colors denote the values of the Spearman correlation coefficients. c Example Spearman correlations and concordance representations of dysregulated proteins from 5xFAD mice (DE.cortex.Age8, DE.hippo.Age5, and DE.hippo.Age8) versus human AD patient data from Drummond 2022 along with human AD data against each other (D22 vs J22, D22 vs J20, J20 vs J22) are shown. The identifiers are denoted analogously to Figs. 2a and 4a. Proteins concordantly up- or downregulated in 5xFAD mice and human AD patient brains are shown in gray quadrants and marked in blue. Proteins of interest with highly significant fold-changes are indicated with gene names. Correlating but non-concordant proteins are marked in brown. d Generation of signatures for proteins concordantly dysregulated in 5xFAD mice and human AD patient brains. The heatmaps show the 15 most down (Sig-, left) or upregulated (Sig + , right) proteins. Colors denote the values of the log2 fold-changes. e Ingenuity pathway analysis (IPA) for the complete set of concordantly dysregulated proteins. The statistical significance of the association between the DEPs and the canonical pathways was measured with a right-tailed Fisher’s exact test to calculate p-values, adjusted by the Benjamini–Hochberg multiple testing correction. All analyses are based on mean values of measured intensities from five biological replicates of tg mice per age and tissue (n = 5)