title: Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease.
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.
authors.affiliation: Institute of Pharmaceutical Science and Institute of Psychiatry, Kings's College London, London, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Whiley
authors.forename: Arundhuti
authors.initials: A
authors.lastname: Sen
authors.forename: James
authors.initials: J
authors.lastname: Heaton
authors.forename: Petroula
authors.initials: P
authors.lastname: Proitsi
authors.forename: Diego
authors.initials: D
authors.lastname: García-Gómez
authors.forename: Rufina
authors.initials: R
authors.lastname: Leung
authors.forename: Norman
authors.initials: N
authors.lastname: Smith
authors.forename: Madhav
authors.initials: M
authors.lastname: Thambisetty
authors.forename: Iwona
authors.initials: I
authors.lastname: Kloszewska
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.forename: Cristina
authors.initials: C
authors.lastname: Legido-Quigley
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism*; D001057:Apolipoproteins E / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism; D015331:Cohort Studies; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D010713:Phosphatidylcholines / Q000378:metabolism*; D011237:Predictive Value of Tests; D012372:ROC Curve
chemical_list: D001057:Apolipoproteins E; D005231:Fatty Acids, Unsaturated; D010713:Phosphatidylcholines
keywords: Addneuromed; Alzheimer's disease; ApoE; Lipid; Mild cognitive impairment; Phosphatidylcholine; Plasma
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