Fig. 1

Study design and metabolic profiling workflow. Plasma and CSF samples were collected concomitantly, from the same subject. Metabolic signatures acquired by the untargeted profiling were explored using the pathway enrichment and topology analysis to identify the biochemical pathways affected in AD. Targeted quantification of metabolites implicated in these identified affected pathways was then performed to obtain the accurate and precise measurement of metabolite concentrations. The clinical phenotype comparison was followed by paired blood plasma vs. CSF comparison and correlation with QAlb to assign the origin of the observed changes. Finally, the associations with known CSF markers of AD pathology were investigated to link the identified changes at the metabolite and pathway level with the clinical outcome. LC-HRMS – liquid chromatography coupled to high-resolution mass spectrometry, LC-MS/MS – liquid chromatography coupled to tandem mass spectrometry, KEGG – Kyoto Encyclopedia of Genes and Genomes, SMPDB – Small Molecule Pathway Data Base