Mass and relative elution time profiling: Two-dimensional analysis of sphingolipids in Alzheimer's disease brains

Leila Hejazi, Jason W H Wong, Danni Cheng, Nicholas Proschogo, Diako Ebrahimi, Brett Garner, Anthony S. Don

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Current lipidomic profiling methods rely mainly on MS to identify unknown lipids within a complex sample. We describe a new approach, involving LCxMS/MS (liquid chromatographyxtandem MS) analysis of sphingolipids based on both mass and hydrophobicity, and use this method to characterize the SM (sphingomyelin), ceramide and GalCer (galactosylceramide) content of hippocampus from AD (Alzheimer's disease) and control subjects. Using a mathematical relationship we exclude the influence of sphingolipid mass on retention time, and generate two-dimensional plots that facilitate accurate visualization and characterization of the different ceramide moieties within a given sphingolipid class, because related molecules align horizontally or vertically on the plots. Major brain GalCer species that differ in mass by only 0.04 Da were easily differentiated on the basis of their hydrophobicity. The importance of our method's capacity to define all of the major GalCer species in the brain samples is illustrated by the novel observation that the proportion of GalCer with hydroxylated fatty acids increased approximately 2-fold in the hippocampus of AD patients, compared with age- and gender-matched controls. This suggests activation of fatty acid hydroxylase in AD. Our method greatly improves the clarity of data obtained in a lipid profiling experiment and can be expanded to other lipid classes.

Original languageEnglish (US)
Pages (from-to)165-175
Number of pages11
JournalBiochemical Journal
Volume438
Issue number1
DOIs
StatePublished - Aug 15 2011

Keywords

  • Alzheimer's disease
  • Ceramide
  • Cerebroside
  • Galactosylceramide
  • Lipidomic analysis
  • Sphingolipid

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