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Fig. 5 | Molecular Neurodegeneration

Fig. 5

From: Network-driven plasma proteomics expose molecular changes in the Alzheimer’s brain

Fig. 5

External Validation. To assess the biological validity of our findings top proteins were cross-referenced at the transcript or genomic level to external datasets containing AD brain mRNA transcriptome data or AD genome-wide association data, respectively. a Pre-frontal cortex transcripts in AD brain corresponding to proteins that correlated with MMSE in our study (see Fig. 3a) correlate strongly with Braak stage or brain atrophy (pre-frontal cortex) beyond what is expected by chance (chi2-test). b Based on meta-data from AD GWAS studies 114 genes which are part of “TGFβ/GDF/BMP signaling” exhibit higher than expected enrichment for significant SNPs (gene-wide p-value using VEGAS; cumulative curve comparison by Kolmogorov–Smirnov test). c Pre-fontal cortex transcripts for 120 genes of the TGFβ/GDF/BMP signaling pathway show many more significant transcript changes in AD than expected by chance (explicit p-value through sample permutation; cumulative curve comparison by Kolmogorov–Smirnov test). d Graphical representation of 92 proteins of TGFβ/GDF/BMP signaling pathway and integration with the findings from the various studies as indicated (only nodes with hits ≥ 1 are shown). Proteins are positioned relative to their location in the cells (extracellular, membrane bound, intracellular) and edges indicate physical or functional interactions (small border diagrams highlight proteins with associated significant changes). e Detailed pathway diagram for GDF-Activin receptor signaling. f Examples of protein (top row) and mRNA changes (bottom row) among the members of the GDF-Activin receptor signaling cascade (all corrected p-values)

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