Fig. 1 The circulatory AD signaling proteome reveals changes in cellular communication. a Overview of the experimental and analysis workflow. Plasma samples were collected at clinical centers, relative protein abundance was determined by antibody microarray and three types of analyses were performed: Protein level, MMSE correlation (cognitive performance), and protein co-secretion analysis. The analyses results were then integrated in a network and pathway enrichment framework and finally subjected to internal and external validation. b Heat map representation of the protein level analysis showing the top 50 most different proteins after unsupervised clustering (q < 0.05), separating samples into AD (pink, right) and controls (blue, left) and proteins into higher in control (blue, top) and higher in AD (pink, bottom). c Volcano-plot showing the distribution of all proteins and naming those significantly different between AD and control subjects (p corr < 0.01). d A network representation of the most significantly changed proteins (p corr < 0.015; un-connected proteins omitted) after integration with known pathway and physical interaction data reveals many densely connected hits in pathways related to TGFβ/GDF/BMP, angiogenesis, and apoptosis signaling. e Example scatter plots of the six top changed proteins (see dashed box in e, mean ± s.e.m; all p-values are corrected for multiple hypothesis testing)