Journal
NEUROBIOLOGY OF AGING
Volume 35, Issue 2, Pages 271-278Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2013.08.001
Keywords
Alzheimer's disease; Phosphatidylcholine; ApoE; Lipid; Plasma; Mild cognitive impairment; Addneuromed
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Funding
- UK NHS National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) for mental health at the South London and Maudsley (SLaM)
- European Commision (AddNeuroMed)
- Waters Centre of Excellence for Mass Spectrometry at King's College London
- Alzheimers Research UK [ART-RF2007-3] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10053] Funding Source: researchfish
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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. (C) 2014 Elsevier Inc. All rights reserved.
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