Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer’s disease

Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid classes previously associated with cardiometabolic disease (phosphatidylethanolamine and triglycerides). We subsequently identified similar lipid signatures in both cohorts with future disease. Lastly, we developed multivariate lipid models that improved classification and prediction. Our results provide a holistic view between the lipidome and AD using a comprehensive approach, providing targets for further mechanistic investigation.

Fast and Quantitative Phospholipidomic Analysis of SH-SY5Y Neuroblastoma Cell Cultures Using LC-MS/MS and 31P NMR

Phospholipid quantification by ³¹P NMR and lipid separation and detection by LC-MS/MS. Fatty acid quantification using scripted reconstruction of elution profile for each fatty acid associated with each lipid species. The combination of NMR and and MS data is complementary and allows better quantification and more complete description than each approach would allow by itself. Datasets exists for both whole-cell and plasma membrane fraction, and we also describe and document the extraction techniques.

Fast and Quantitative Phospholipidomic Analysis of SH-SY5Y Neuroblastoma Cell Cultures Using LC-MS/MS and 31P NMR

Phospholipid quantification by ³¹P NMR and lipid separation and detection by LC-MS/MS. Fatty acid quantification using scripted reconstruction of elution profile for each fatty acid associated with each lipid species. The combination of NMR and and MS data is complementary and allows better quantification and more complete description than each approach would allow by itself. Datasets exists for both whole-cell and plasma membrane fraction, and we also describe and document the extraction techniques.

Fast and Quantitative Phospholipidomic Analysis of SH-SY5Y Neuroblastoma Cell Cultures Using LC-MS/MS and 31P NMR

Phospholipid quantification by ³¹P NMR and lipid separation and detection by LC-MS/MS. Fatty acid quantification using scripted reconstruction of elution profile for each fatty acid associated with each lipid species. The combination of NMR and and MS data is complementary and allows better quantification and more complete description than each approach would allow by itself. Datasets exists for both whole-cell and plasma membrane fraction, and we also describe and document the extraction techniques.