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Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease

Whiley, L.ORCID: 0000-0002-9088-4799, 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. and Legido-Quigley, C. (2014) Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease. Neurobiology of Aging, 35 (2). pp. 271-278.

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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.

Item Type: Journal Article
Publisher: Elsevier Inc
Copyright: © 2014 Elsevier Inc.
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