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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.

Original publication

DOI

10.1016/j.neurobiolaging.2013.08.001

Type

Journal article

Journal

Neurobiol Aging

Publication Date

02/2014

Volume

35

Pages

271 - 278

Keywords

Addneuromed, Alzheimer's disease, ApoE, Lipid, Mild cognitive impairment, Phosphatidylcholine, Plasma, Alzheimer Disease, Apolipoproteins E, Chromatography, Liquid, Cognitive Dysfunction, Cohort Studies, Fatty Acids, Unsaturated, Female, Humans, Magnetic Resonance Spectroscopy, Male, Mass Spectrometry, Phosphatidylcholines, Predictive Value of Tests, ROC Curve