Fig. 9.

AD plasma protein co-expression network. A-C Control (n=18) and AD (n=18) plasma samples from n=35/36 of the same subjects from which the CSF network was generated were similarly analyzed by TMT-MS, Olink, and Somalogic proteomic platforms, and a protein co-expression network was constructed using the union protein measurements harmonized across all three platforms (n=7284 SomaScan, 1140 Olink, and 1165 TMT-MS depleted protein measurements, total n=9589 measurements, n=6614 unique gene symbols). The network consisted of 35 protein co-expression modules. Nine of the 35 modules that were most highly correlated to CSF pathological or cognitive traits are in bold, with the two most strongly trait-related modules highlighted in red. Module eigenprotein correlations with traits, preservation analyses, eigenprotein differences between AD and control, and cell type overlap tests were performed in the same fashion as the CSF network as described in Fig. 8. Correlation was performed with CSF levels of T-Tau, p-Tau181, Aβ42, and Aβ42/T-Tau ratio. B The 42 proteins comprising the M33 Adhesions/ECM/Wound Response module. Larger nodes represent larger kME values, or module hubs. Module proteins are highlighted according to the proteomic platform in which they were measured. C M33 Adhesion/ECM/Wound Response levels between control and AD (top panels), and eigenprotein correlation with MoCA and CSF p-Tau181 (middle panels) and T-tau and Aβ42/T-tau levels (bottom panels). Further information on the plasma network is provided in Additional file 2: Supplementary Tables 20 and 21, and Additional file 1: Extended Data. Boxplots represent the median, 25th, and 75th percentiles, and box hinges represent the interquartile range of the two middle quartiles within a group. Datapoints up to 1.5 times the interquartile range from box hinge define the extent of whiskers (error bars). Differences between groups were assessed by t test or one-way ANOVA with Tukey test. Correlations were performed using Pearson correlation