Targeted Lipidomics of Fontal Cortex and Plasma Diacylglycerols (DAG) in Mild Cognitive Impairment and Alzheimer's Disease: Validation of DAG Accumulation Early in the Pathophysiology of Alzheimer's Disease

Paul L. Wood, Srikanth Medicherla, Naveen Sheikh, Bradley Terry, Aaron Phillipps, Jeffrey A. Kaye, Joseph F. Quinn, Randall L. Woltjer

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Previous studies have demonstrated augmented levels of diacylglycerols (DAG) in the frontal cortex and plasma of Alzheimer's disease (AD) patients. We extended these findings from non-targeted lipidomics studies to design a lipidomics platform to interrogate DAGs and monoacylglycerols (MAG) in the frontal cortex and plasma of MCI subjects. Control subjects included both aged normal controls and controls with normal cognition, but AD pathology at autopsy, individuals termed nondemented AD neuropathology. DAGs with saturated, unsaturated, and polyunsaturated fatty acid substituents were found to be elevated in MCI frontal cortex and plasma. Tandem mass spectrometry of the DAGs did not reveal any differences in the distributions of the fatty acid substitutions between MCI and control subjects. While triacylglycerols were not altered in MCI subjects there were increases in MAG levels both in the frontal cortex and plasma. In toto, increased levels of DAGs and MAGs appear to occur early in AD pathophysiology and require both further validation in a larger patient cohort and elucidation of the lipidomics alteration(s) that lead to the accumulation of DAGs in MCI subjects.

Original languageEnglish (US)
Pages (from-to)537-546
Number of pages10
JournalJournal of Alzheimer's Disease
Volume48
Issue number2
DOIs
StatePublished - Sep 9 2015

Keywords

  • Alzheimer's disease
  • diacylglycerols
  • mild cognitive impairment
  • monoacylglycerols

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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