Evidence of altered phosphatidylcholine metabolism in Alzheimer's disease

NEUROBIOLOGY OF AGING

卷:35

Article

Whiley, Luke^1,2  Sen, Arundhuti^1,2  Heaton, James³  Proitsi, Petroula^1,2  Garcia-Gomez, Diego⁴  Leung, Rufina^1,2  Smith, Norman³  Thambisetty, Madhav⁵  Kloszewska, Iwona⁶  Mecocci, Patrizia⁷  Soininen, Hilkka^8,9  Tsolaki, Magda¹⁰  Vellas, Bruno¹¹  Lovestone, Simon^1,2  Legido-Quigley, Cristina^1,2 

[1] Kings Coll London, Inst Pharmaceut Sci, London SE1 9NH, England

[2] Kings Coll London, Inst Psychiat, London SE1 9NH, England

[3] Kings Coll London, Waters Ctr Innovat, London SE1 9NH, England

[4] Univ Salamanca, Dept Analyt Chem, E-37008 Salamanca, Spain

[5] NIA, Clin & Tanslat Neurosci Unit, Lab Behav Neurosci, Baltimore, MD 21224 USA

[6] Med Univ Lodz, Dept Old Age Psychiat & Psychot Disorders, Lodz, Poland

[7] Univ Perugia, Dept Clin & Expt Med, Sect Gerontol & Geriatr, I-06100 Perugia, Italy

[8] Univ Eastern Finland, Dept Neurol, Kuopio, Finland

[9] Kuopio Univ Hosp, SF-70210 Kuopio, Finland

[10] Aristotle Univ Thessaloniki, Dept Neurol 3, GR-54006 Thessaloniki, Greece

[11] Hop Toulouse, Dept Internal & Geriatr Med, Toulouse, France

关键词: Alzheimer's disease;    Phosphatidylcholine;    ApoE;    Lipid;    Plasma;    Mild cognitive impairment;    Addneuromed;   

DOI  :  10.1016/j.neurobiolaging.2013.08.001

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free