Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease.
Title | Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Whiley, L., Sen A., Heaton J., Proitsi P., García-Gómez D., Leung R., Smith N., Thambisetty M., Kloszewska I., Mecocci P., Soininen H., Tsolaki M., Vellas B., Lovestone S., & Legido-Quigley C. |
Corporate Authors | AddNeuroMed Consortium |
Journal | Neurobiol Aging |
Volume | 35 |
Issue | 2 |
Pagination | 271-8 |
Date Published | 2014 Feb |
ISSN | 1558-1497 |
Keywords | Alzheimer Disease, Apolipoproteins E, Chromatography, Liquid, Cohort Studies, Fatty Acids, Unsaturated, Female, Humans, Magnetic Resonance Spectroscopy, Male, Mass Spectrometry, Mild Cognitive Impairment, Phosphatidylcholines, Predictive Value of Tests, ROC Curve |
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. |
DOI | 10.1016/j.neurobiolaging.2013.08.001 |
Alternate Journal | Neurobiol. Aging |
PubMed ID | 24041970 |
Grant List | NF-SI-0512-10053 / / Department of Health / United Kingdom |