Association of blood lipids with Alzheimer's disease: A comprehensive lipidomics analysis

被引:139
作者
Proitsi, Petroula [1 ]
Kim, Min [2 ]
Whiley, Luke [2 ,14 ]
Simmons, Andrew [1 ,3 ,4 ]
Sattlecker, Martina [1 ,3 ,4 ]
Velayudhan, Latha [1 ]
Lupton, Michelle K. [5 ]
Soininen, Hillka [6 ,7 ]
Kloszewska, Iwona [8 ]
Mecocci, Patrizia [9 ]
Tsolaki, Magda [10 ]
Vellas, Bruno [11 ]
Lovestone, Simon [12 ]
Powell, John F. [1 ]
Dobson, Richard J. B. [1 ,3 ,4 ,13 ]
Legido-Quigley, Cristina [2 ]
机构
[1] Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England
[2] Kings Coll London, Inst Pharmaceut Sci, London, England
[3] South London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, London, England
[4] South London & Maudsley NHS Fdn Trust, Biomed Res Unit Dementia, London, England
[5] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia
[6] Kuopio Univ Hosp, Dept Neurol, Kuopio, Finland
[7] Univ Eastern Finland, Kuopio, Finland
[8] Med Univ Lodz, Dept Old Age Psychiat & Psychot Disorders, Lodz, Poland
[9] Univ Perugia, Dept Med, Sect Gerontol & Geriatr, Perugia, Italy
[10] Aristotle Univ Thessaloniki, Memory & Dementia Ctr, Thessaloniki, Greece
[11] Hop Toulouse, Gerontopole, INSERM U 1027, Dept Internal & Geriatr Med, Toulouse, France
[12] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England
[13] UCL, UCL Inst Hlth Informat, Farr Inst Hlth Informat Res, London, England
[14] Imperial Coll London, Dept Surg & Canc, MRC NIHR Natl Phenome Ctr, IRDB Bldg,Du Cane Rd, London W12 0NN, England
基金
英国工程与自然科学研究理事会; 英国医学研究理事会; 欧盟第七框架计划; 英国惠康基金; 英国经济与社会研究理事会;
关键词
Alzheimer's disease; Dementia; Brain atrophy; sMRI; Rate of cognitive decline; Lipidomics; Metabolomics; Biomarkers; Machine learning; Multivariate; Classification; Random forest; CEREBROSPINAL-FLUID; ER MEMBRANES; PLASMA; RISK; BIOMARKERS; DISCOVERY; IDENTIFICATION; DYSLIPIDEMIA; EPIDEMIOLOGY; TECHNOLOGY;
D O I
10.1016/j.jalz.2016.08.003
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Introduction: The aim of this study was to (1) replicate previous associations between six blood lipids and Alzheimer's disease (AD) (Proitsi et al 2015) and (2) identify novel associations between lipids, clinical AD diagnosis, disease progression and brain atrophy (left/right hippocampus/entorhinal cortex). Methods: We performed untargeted lipidomic analysis on 148 AD and 152 elderly control plasma samples and used univariate and multivariate analysis methods. Results: We replicated our previous lipids associations and reported novel associations between lipids molecules and all phenotypes. A combination of 24 molecules classified AD patients with >70% accuracy in a test and a validation data set, and we identified lipid signatures that predicted disease progression (R-2 = 0.10, test data set) and brain atrophy (R-2 >= 0.14, all test data sets except left entorhinal cortex). We putatively identified a number of metabolic features including cholesteryl esters/triglycerides and phosphatidylcholines. Discussion: Blood lipids are promising AD biomarkers that may lead to new treatment strategies.(C) 2016 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
引用
收藏
页码:140 / 151
页数:12
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