Lipidomic Analysis of Postmortem Prefrontal Cortex Phospholipids Reveals Changes in Choline Plasmalogen Containing Docosahexaenoic Acid and Stearic Acid Between Cases With and Without Alzheimer’s Disease

Yurika Otoki, Shunji Kato, Kiyotaka Nakagawa, Danielle J. Harvey, Lee Way Jin, Britany N. Dugger, Ameer Y. Taha

Research output: Contribution to journalArticlepeer-review

Abstract

Alzheimer’s disease (AD) is a progressive and incurable brain disorder that has been associated with structural changes in brain phospholipids (PLs), including diacyl species and ether-linked PLs known as plasmalogens. Most studies have characterized total changes in brain PL pools (e.g., choline plasmalogens), particularly in prefrontal cortex, but detailed and quantitative information on the molecular PL species impacted by the disease is limited. In this study, we used a comprehensive mass-spectrometry method to quantify diacyl and plasmalogen species, alkyl synthetic precursors of plasmalogens, and lysophospholipid degradation products of diacyl and plasmalogen PLs, in postmortem samples of prefrontal cortex from 21 AD patients and 20 age-matched controls. Total PLs were also quantified with gas-chromatography analysis of bound fatty acids following thin layer chromatography isolation. There was a significant 27% reduction in the concentration (nmol/g wet weight) of choline plasmalogen containing stearic acid (alkenyl group) and docosahexaenoic acid in AD compared to controls. Stearic acid concentration in total PLs was reduced by 26%. Our findings suggest specific changes in PLs containing stearic acid and docosahexaenoic acid in AD prefrontal cortex, highlighting structural and turnover PL pathways that could be targeted.

Original languageEnglish (US)
JournalNeuroMolecular Medicine
DOIs
StateAccepted/In press - 2021

Keywords

  • Alkyl-acyl phospholipids
  • Alzheimer’s disease
  • Lipids
  • Lysophospholipids
  • Plasmalogens
  • Prefrontal cortex

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience

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