Fig. 1

Correlational Network Analysis. a, b Proteins in frontal cortex from Alzheimer’s, asymptomatic Alzheimer’s, and control brains were analyzed by tandem mass spectrometry and quantified using either a label-free (LFQ)-based or tandem mass tag (TMT)-based quantification pipeline. The resulting data from each quantification approach were used to build separate correlational protein networks. a Modules in the LFQ-trypsin and TMT-LysC networks are represented by numbers (1–16 in LFQ and 1–50 in TMT) and a cognate color, and the correlational relationship among the different modules within a network is represented by dendrogram. The overlap of proteins within each TMT-LysC module with cell type specific protein markers from microglia, astrocytes, oligodendrocytes (oligo), and neurons is shown by single color heat map (increased red represents increased overlap). Correlation between modules and neuritic amyloid plaque burden (CERAD score) and tau tangle burden (Braak stage) is shown by two-color heat map for both TMT-LysC and LFQ-trypsin networks (red represents positive correlation, blue represents negative correlation). The CERAD score captures the type of amyloid plaque burden most closely associated with cognitive decline [53]. Module protein membership overlap between TMT-LysC and LFQ-trypsin modules is shown by two-color heat map in the large box (red indicates more overlap than expected, blue indicates less overlap than expected), with a summary of maximal overlap for each module with all other modules in the other network shown by single color heatmap in boxes labeled “Max”. All modules in the LFQ-trypsin network were preserved in the TMT-LysC network prior to correction for multiple comparisons. Preservation of LFQ-trypsin modules 7 and 15 in the TMT-LysC network was no longer significant after correction for multiple comparisons. The area highlighted by the dotted line box represents TMT-LysC modules that have little to no overlap in protein membership with LFQ-trypsin modules, representing protein modules unique to the TMT-LysC network. b Percent novelty of protein members within each module of the TMT-LysC network compared to the LFQ-trypsin network. Bars are color coded by heatmap for degree of significance by P value. P values shown in (a) and (b) are corrected by Benjamini-Hochberg FDR