TY - JOUR
T1 - Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease
AU - Whiley, Luke
AU - Sen, Arundhuti
AU - Heaton, James
AU - Proitsi, Petroula
AU - García-Gómez, Diego
AU - Leung, Rufina
AU - Smith, Norman
AU - Thambisetty, Madhav
AU - Kloszewska, Iwona
AU - Mecocci, Patrizia
AU - Soininen, Hilkka
AU - Tsolaki, Magda
AU - Vellas, Bruno
AU - Lovestone, Simon
AU - Legido-Quigley, Cristina
AU - AddNeuroMed Consortium
N1 - Copyright © 2014 Elsevier Inc. All rights reserved.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - Alzheimer Disease/etiology
KW - Apolipoproteins E/blood
KW - Chromatography, Liquid/methods
KW - Cognitive Dysfunction/etiology
KW - Cohort Studies
KW - Fatty Acids, Unsaturated/blood
KW - Female
KW - Humans
KW - Magnetic Resonance Spectroscopy/methods
KW - Male
KW - Mass Spectrometry/methods
KW - Phosphatidylcholines/metabolism
KW - Predictive Value of Tests
KW - ROC Curve
U2 - 10.1016/j.neurobiolaging.2013.08.001
DO - 10.1016/j.neurobiolaging.2013.08.001
M3 - Journal article
C2 - 24041970
SN - 0197-4580
VL - 35
SP - 271
EP - 278
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 2
ER -