Fig. 1.

Experimental pipeline overview. Initially a typical liquid chromatography–mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) metabolite screen led to the identification of 3 phosphatidylcholine (PC) molecules that significantly decrease in individuals with Alzheimer’s disease (AD) compared to controls. This led to a comprehensive multiplatform lipidomic analysis consisting of 3 major components. During NMR analysis of patient plasma, particular attention was focused on total choline-containing molecules, a vital component of the phosphatidylcholine molecules identified in the screen experimental section. LC-MS analysis of plasma fatty acids (arachidonic acid, docosahexaenoic acid, and eicosapentaenoic acid) was also conducted. Again, as with NMR analysis of choline species, these fatty acid species are components of phosphatidylcholine structures indentified in the screen experimental section. Finally, comprehensive lipidomic validation was conducted with a large sample cohort. Here a specially developed lipidomic LC-MS method was applied to increased sample numbers. The method is able to detect >3000 lipid markers from a single plasma extraction.