Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease

Luke Whiley, Arundhuti Sen, James Heaton, Petroula Proitsi, Diego Garcia-Gomez, Rufina Leung, Norman Smith, Madhav Thambisetty, Iwona Kloszewska, Patrizia Mecocci, Hilkka Soininen, Magda Tsolaki, Bruno Vellas, Simon Lovestone, Cristina Legido Quigley

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224 Citations (Scopus)
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Abstract

Abberant lipid metabolism is implicated in Alzheimer's disease (AD) pathophysiology, but the connections between AD and lipid metabolic pathways are not fully understood. To investigate plasma lipids in AD, a multiplatform screen (n = 35 by liquid chromatography–mass spectrometry and n = 35 by nuclear magnetic resonance) was developed, which enabled the comprehensive analysis of plasma from 3 groups (individuals with AD, individuals with mild cognitive impairment (MCI), and age-matched controls). This screen identified 3 phosphatidylcholine (PC) molecules that were significantly diminished in AD cases. In a subsequent validation study (n = 141), PC variation in a bigger sample set was investigated, and the same 3 PCs were found to be significantly lower in AD patients: PC 16:0/20:5 (p < 0.001), 16:0/22:6 (p < 0.05), and 18:0/22:6 (p < 0.01). A receiver operating characteristic (ROC) analysis of the PCs, combined with apolipoprotein E (ApoE) data, produced an area under the curve predictive value of 0.828. Confirmatory investigations into the background biochemistry indiciated no significant change in plasma levels of 3 additional PCs of similar structure, total choline containing compounds or total plasma omega fatty acids, adding to the evidence that specific PCs play a role in AD pathology.
Original languageEnglish
Pages (from-to)271-278
Number of pages8
JournalNeurobiology of Aging
Volume35
Issue number2
Early online date13 Sept 2013
DOIs
Publication statusPublished - 1 Feb 2014

Keywords

  • Alzheimer's disease
  • Phosphatidylcholine
  • ApoE
  • Lipid
  • Plasma
  • Mild cognitive impairment
  • Addneuromed
  • PHOSPHOLIPASE A(2) ACTIVITY
  • TANDEM MASS-SPECTROMETRY
  • COGNITIVE IMPAIRMENT
  • PLASMA
  • LIPIDS
  • PROGRESSION
  • BIOMARKERS
  • MS
  • IDENTIFICATION
  • SPECTROSCOPY
  • Acknowledged-BRU
  • Acknowledged-BRU-13/14
  • Acknowledged-BRC

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