Fig. 6

Integration of CSF, serum, and cortex datasets elucidates consistent mitochondrial signatures in Alzheimer’s disease across proteomes. a Summary of the DE analysis of serum proteome, and its integration with CSF and cortex proteome. Four thousand eight hundred twenty-six proteins were quantified in AD serum samples. Three hundred ninety-five proteins were identified as differentially expressed proteins with a Z-score transformed log2 fold difference > 2 and p value < 0.05. One hundred seven out of these proteins are differentially expressed in both serum and CSF proteomes, 94 of these proteins are differentially expressed in both serum and brain proteomes, 37 proteins are differentially expressed in serum, CSF, and Cortex proteome. Twenty-two out of the 37 DE proteins are mitochondrial proteins. b Deep serum proteome analysis identifies decrease of mitochondrial proteins. The X-axis of the volcano plot shows the Z score transformed log2 fold change comparing AD to Ctl and Y-axis indicates -log10 p value. Top DE proteins in serum are plotted in black and labeled. Proteins that are differentially expressed in human CSF, mouse CSF, and human serum proteomes are plotted in red and labeled. Red dashed lines indicate the DE cutoff of p value < 0.05 and Z value difference > 2. c Integration of serum and CSF proteomes identifies consistent and massive mitochondrial protein decrease. Proteins that are quantified in both serum and CSF are plotted as a function of their Z values comparing AD to Ctl in CSF (x-axis) and in serum (y-axis). Fifty-five non-mitochondrial DE proteins with Z value difference > 2 and FDR < 0.2 in CSF or p value < 0.05 in serum are plotted in black, and 52 mitochondrial DE proteins are plotted in red. Names of two mitochondrial proteins that were applied for TOMAHAQ targeted MS assay (Fig. 8) were labeled. Red dashed lines indicate Z value difference > 2 in CSF and serum. d Integration of serum and cortex proteomes unveils mitochondrial protein changes and amyloid-correlated protein panel. Proteins that are quantified in both serum and cortex are plotted as a function of their Z value change comparing AD to Ctl in cortex (x-axis) and in serum (y-axis). Seventy non-mitochondrial DE proteins with Z value difference > 2 and FDR < 0.2 in cortex or p value < 0.05 in serum were plotted in black. Three top DE proteins that were reported in the amyloid-correlated protein panel in previous cortex study were labeled.Twenty-four mitochondrial DE proteins are plotted in red. Red dashed lines indicate Z value difference > 2 in serum and cortex. e Expression levels of representative DE proteins in cortex and serum. Dot plots overlaid onto boxplots showing expression of representative DE proteins in cortex, CSF, and serum proteomes. The p values of the DE analyses between AD and healthy control are displayed on the top of the plots. DE analyses were carried out through the LIMMA R package. X-axis shows sample groups, y-axis indicates Log2 transformed TMT intensity. Boxplot center line, median; box limits, upper and lower quartiles; whiskers, 1.5x interquartile range; points, expression levels of each individual samples