Figure 4.

APOE4 alters protein levels at the BBB. (A) Distribution of functional groups for all proteins found to be differentially expressed in brain capillaries from E4F compared with E3F mice at 7 mo of age. Legend shows abundant functional groups with number of differentially expressed proteins per functional group indicated. (B) Percentage distribution of upregulated and downregulated proteins within abundant functional groups found to be differentially regulated. (C) Heatmap showing hierarchical clustering of single-cell RNA-seq gene expression for all proteins found to be differentially regulated in brain capillary ECs and PCs. Proteins showing preferential cell-type enrichment are assigned to either ECs or PCs as highlighted by blue brackets. The gene names encoding differentially expressed proteins assigned to ECs, PCs, or astrocyte end feet are given in Table S1 L. z-Scores for proteins enriched in ECs and PCs are reported in Table S1 M. (D) Distribution of functional groups within brain capillary ECs and PCs assigned to differentially expressed proteins. Legend shows abundant functional groups with the number of differentially expressed proteins for the most abundant functional groups in the EC and PC pie charts indicated. Proteins assigned to astrocyte end feet are excluded from analysis. All data in A–D are from four mice per group. (E) PPIs extracted from BioGRID data are assigned to proteins regulated by either phosphorylation or expression within brain capillary ECs and PCs and converge on common cellular processes. Proteins were clustered according to their involvement in particular cellular processes, demarcated by the colored regions. Each node represents a single dysregulated protein by either phosphorylation and/or expression level within the disrupted PPI signaling network in ECs and PCs. The color-coded legend shows direction (up or down) and type of dysregulation (phosphorylation or protein level), with the number of dysregulated proteins indicated. For full description of dysregulated PPI signaling networks in ECs and PCs, see the main text. ECM, extracellular matrix.