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Plasma lipidomics analysis finds long chain cholesteryl esters to be associated with Alzheimer's disease

Research output: Contribution to journalArticle

P Proitsi ; M Kim ; L Whiley ; M Pritchard ; R Leung ; H Soininen ; I Kloszewska ; P Mecocci ; M Tsolaki ; B Vellas ; P Sham ; S Lovestone ; J F Powell ; R J B Dobson ; C Legido-Quigley

Original languageEnglish
Article numbere494
Number of pages8
JournalTranslational psychiatry
Volume5
DOIs
StatePublished - 13 Jan 2015

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  • Proitsi el al. 2015

    Proitsi_el_al._2015.pdf, 697 KB, application/pdf

    24/03/2016

    Final published version

    CC BY

King's Authors

Abstract

There is an urgent need for the identification of Alzheimer’s disease (AD) biomarkers. Studies have now suggested the promising use of associations with blood metabolites as functional intermediate phenotypes in biomedical and pharmaceutical research. The aim of this study was to use lipidomics to identify a battery of plasma metabolite molecules that could predict AD patients from controls. We performed a comprehensive untargeted lipidomic analysis, using ultra-performance liquid chromatography/mass spectrometry on plasma samples from 35 AD patients, 40 elderly controls and 48 individuals with mild cognitive impairment (MCI) and used multivariate analysis methods to identify metabolites associated with AD status. A combination of 10 metabolites could discriminate AD patients from controls with 79.2% accuracy (81.8% sensitivity, 76.9% specificity and an area under curve of 0.792) in a novel test set. Six of the metabolites were identified as long chain cholesteryl esters (ChEs) and were reduced in AD (ChE 32:0, odds ratio (OR)=0.237, 95% confidence interval (CI)=0.10–0.48, P=4.19E−04; ChE 34:0, OR=0.152, 95% CI=0.05–0.37, P=2.90E−04; ChE 34:6, OR=0.126, 95% CI=0.03–0.35, P=5.40E−04; ChE 32:4, OR=0.056, 95% CI=0.01–0.24, P=6.56E−04 and ChE 33:6, OR=0.205, 95% CI=0.06–0.50, P=2.21E−03, per (log2) metabolite unit). The levels of these metabolites followed the trend control>MCI>AD. We, additionally, found no association between cholesterol, the precursor of ChE and AD. This study identified new ChE molecules, involved in cholesterol metabolism, implicated in AD, which may help identify new therapeutic targets; although, these findings need to be replicated in larger well-phenotyped cohorts.

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