Fig. 2

Ultra-deep CSF proteome profiling identifies evident mitochondrial protein reduction in Alzheimer’s disease. a Workflow for CSF proteome analysis. b Ultra-deep CSF proteome unveiled evident decrease of mitochondrial proteins in AD. The X-axis of the volcano plot for all quantified CSF proteins shows the Z score transformed log2 level fold changes comparing AD to Ctl. Y-axis shows the -log10 level FDR value. Previously reported AD CSF biomarkers are plotted in black. Top DE proteins with FDR < 0.01 and Z value < − 5 are plotted in red. Red dashed lines indicate the DE cutoff of FDR < 0.05 and Z score difference > 2. c Majority of top DEs are mitochondrial proteins showing decreased level in AD. Heatmap shows the relative expression of top DE proteins with Z score difference > 5 and FDR < 0.01 comparing AD to Ctl, these DE proteins are classified into distinct groups (a-e) according to their mitochondrial functions as indicated on the right side of the heatmap. d Pie chart shows the mitochondrial functional groups classified in panel c. The number of proteins in each subgroup is labeled. e Deep profiling depth is a prerequisite for confident detection of evident mitochondrial protein changes. CSF proteins are plotted as a function of their concentration rank (x-axis) and their mean log10 level TMT intensity in all samples (y-axis). Top DE mitochondrial proteins with Z score difference > 5 and FDR < 0.01 were plotted in red. The median concentration rank of these mitochondrial proteins is labeled and marked by dashed red line