Fig. 3

Identification of Aβ-correlated and anticorrelated protein alterations in 5xFAD brains. a Numbers of proteins that correlate (corr, in red) or anticorrelate (acorr, in blue) with Aβ aggregates in hippocampus and cortex and are differentially expressed at 2 (DE.cortex.Age2, DE.hippo.Age2), 5 (DE.cortex.Age5, DE.hippo.Age5), or 8 (DE.cortex.Age8, DE.hippo.Age8) months. The identifiers were denoted analogously as in Fig. 2a. The degree of correlation was assessed by Pearson correlation and corresponding FDR-adjusted p-values. b Volcano plots depicting the protein expression logarithmic fold-changes (log10 fold-change, x-axis) and the adjusted p-values (− log10 p-value, y-axis) across all time points (age 2, 5, and 8 months) for DEPs that correlate (corr) or anticorrelate (acorr) with Aβ aggregates in hippocampus (h) and cortex (c). All proteins highlighted in blue are expressed significantly differently. The Aβ-correlating AD biomarker candidate Arl8b is marked in red. Proteins of interest with highly significant fold-changes are indicated with gene names. Proteins not significantly changed are highlighted in gray. Significance was determined using a two-tailed t-test and a Benjamini–Hochberg False Discovery Rate (FDR) set to 5%. c, d Changes of APOE transcript (c) and protein (d) levels in hippocampus (H) and cortex (C) of 2-, 5-, and 8-month-old 5xFAD mice. LFC, log2 fold-change. e Number of differentially expressed genes (DEGs, light red) that overlap (purple) with Aβ aggregate-correlated (corr) and anticorrelated (acorr) DEPs (light blue). f Time-dependent changes in the abundance of 9 correlating or anticorrelating molecules; both protein (top) and transcript (bottom) level changes are shown. The temporal changes of the t-scores across all ages (2, 5, and 8 months) in cortex (orange) and hippocampus (blue) are illustrated. The statistical significance of differentially expressed proteins and transcripts was measured with a two-tailed t-test, adjusted by the Benjamini–Hochberg multiple testing correction (*, p < 0.05, **, p < 0.01; ***, p < 0.001). g Ingenuity pathway analysis (IPA) for the correlating or anticorrelating molecules that are changed both at the protein and transcript level as shown in panels e and f. The statistical significance of the association between the DEPs and the canonical pathways was measured with right-tailed Fisher’s exact test to calculate the 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)