A more detailed lipidomics method was applied in the ADNI-1 samples to obtain better coverage of the sphingolipidome. Methodology on the ADNI cohort was as described by Huynh et al.21 (link). In brief, extracted samples were run using reverse phase liquid chromatography coupled with a triple quadrupole mass spectrometer (Agilent 6490, Agilent). Characterization of sphingolipid isomers has been reported previously82 (link) where repeated pooled runs using differing mass spectrometry conditions to obtain structurally informative fragments in MS/MS. Ratios were generated using 112 sphingolipid species and log2-transformed. Linear regression with ADAS-Cog. 13 was done with age, sex, BMI, HDL-C, total cholesterol, clinical triglycerides, fasting status, and APOE e4 genotype as covariates. p-values were corrected for multiple correction comparison using the Benjamini and Hochberg approach83 .
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