期刊
ALZHEIMERS & DEMENTIA
卷 14, 期 6, 页码 723-733出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jalz.2018.01.003
关键词
Dementia; Alzheimer's disease; Metabolomics; Biomarkers; Amino acids
资金
- National Institute for Health and Welfare
- Academy of Finland [139635, 136895, 263836, 294834]
- Finnish Foundation for Cardiovascular Research
- National Institute for Health and Welfare (THL)
- Finnish Centre for Pensions (ETK)
- Social Insurance Institution of Finland (KELA)
- Local Government Pensions Institution (KEVA)
- European Union H2020 [692145]
- Est. RC [IUT20-60, PUT1665P]
- EU [2014-2020.4.01.15-0012]
- Estonian Ministry of Social Affairs
- Centre for Medical Systems Biology (CMSB)
- Netherlands Consortium for Systems Biology (NCSB)
- EUROSPAN [018947, LSHG-CT-2006-01947]
- European Community's Seventh Framework Programme [HEALTH-F42007-201413]
- Quality of Life and Management of the Living Resources of 5th Framework Programme [QLG2-CT2002-01254]
- EUROHEADPAIN [602633]
- Internationale Stichting Alzheimer Onderzoek (ISAO)
- Hersenstichting Nederland (HSN)
- PND under project PERADES [733051021]
- Biobanking and Biomolecular Resources Research Infrastructure (BBMRI)-NL [184.021.007]
- Veni grant from ZonMw
- Cardio Vasculair Onderzoek Nederland [CVON2012-03]
- BBMRINL
- Dutch government (NWO) [184.021.007, 184033111]
- Netherlands Organisation for Health Research and Development (ZonMW) as part of the Joint Programming for Neurological Disease (JPND) as part of the program PERADES [733051021]
- European Union Innovative Medicine Initiative (IMI) programme as part of the Alzheimer Disease Apolipoprotein Pathology for Treatment Elucidation and Development (ADAPTED) [115975]
- European Union's Horizon 2020 research and innovation programme as part of the Common mechanisms and pathways in Stroke and Alzheimer's disease (CoSTREAM) project [667375]
- European Union's Horizon 2020 research and innovation programme Marie Sklodowska-Curie Research and Innovation Staff Exchange (RISE) as part of the Personalized pREvention of Chronic DIseases (PRECeDI) project [645740]
- European Research Council (ERC) [678543]
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands Organization for Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DG XII)
- municipality of Rotterdam
- Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]
- Genetic Laboratory of the Department of Internal Medicine, Erasmus MC
- Research Institute for Diseases in the Elderly [014-93-015]
- Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- Genetic Laboratory of the Department of Internal Medicine
- Department of Forensic Molecular Biology
- Department of Dermatology, Erasmus MC, Rotterdam, Netherlands
- UK Medical Research Council [K013351, G0902037, MC_UU_1201/1]
- British Heart Foundation
- US National Institutes of Health [R01HL36310, R01AG013196]
- National Institute on Aging [R01 AG054076, AG016495, AG049505, AG049607, AG033193]
- National Institute of Neurological Disorders and Stroke [NS017950]
- National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK-HL081572]
- National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195, HHSN268201500001I]
- Novo Nordisk Foundation
- Sigrid Juselius Foundation
- University of Oulu
- University of Bristol
- MRC [MR/R024227/1, G0902037, MR/K013351/1] Funding Source: UKRI
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL036310, R01HL081572] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS017950, UH2NS100605] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG054076, R01AG033193, R01AG013196, R01AG033040, R01AG016495, R01AG008122, R01AG049607, R01AG031287, U01AG049505, U01AG052409] Funding Source: NIH RePORTER
Introduction: Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia and Alzheimer's disease. Methods: We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four cohorts were used for discovery with replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented. Results: Over 246,698 person-years, 995 and 745 cases of incident dementia and Alzheimer's disease were detected, respectively. Three branched-chain amino acids (isoleucine, leucine, and valine), creatinine and two very low density lipoprotein (VLDL)-specific lipoprotein lipid subclasses were associated with lower dementia risk. One high density lipoprotein (HDL; the concentration of cholesterol esters relative to total lipids in large HDL) and one VLDL (total cholesterol to total lipids ratio in very large VLDL) lipoprotein lipid subclass was associated with increased dementia risk. Branched-chain amino acids were also associated with decreased Alzheimer's disease risk and the concentration of cholesterol esters relative to total lipids in large HDL with increased Alzheimer's disease risk. Discussion: Further studies can clarify whether these molecules play a causal role in dementia pathogenesis or are merely markers of early pathology. (C) 2018 The Authors. Published by Elsevier Inc. on behalf of the Alzheimer's Association.
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