Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease
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- 作者：Luke Whiley ; Arundhuti Sen ; James Heaton ; Petroula Proitsi ; Diego Garc铆a-G贸mez ; Rufina Leung ; Norman Smith ; Madhav Thambisetty ; Iwona Kloszewska ; Patrizia Mecocci ; Hilkka Soininen ; Magda Tsolaki ; Bruno Vellas ; Simon Lovestone ; Cristina Legido-Quigley ; AddNeuroMed Consortium
- 关键词：Alzheimer's disease ; Phosphatidylcholine ; ApoE ; Lipid ; Plasma ; Mild cognitive impairment ; Addneuromed
- 刊名：Neurobiology of Aging
- 出版年：February, 2014
- 年：2014
- 卷：35
- 期：2
- 页码：271-278
- 全文大小：1395 K
文摘
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聽= 35 by liquid chromatography-mass spectrometry and n聽= 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聽= 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.