期刊
NEUROBIOLOGY OF AGING
卷 84, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2019.05.008
关键词
TREM2; MS4A6A; Alzheimer's disease; Genome-wide association study
资金
- National Natural Science Foundation of China [91849126]
- National Key R&D Program of China [2018YFC1314700]
- Shanghai Municipal Science and Technology Major Project [2018SHZDZX01]
- Zhangjiang Lab, Tianqiao and Chrissy Chen Institute
- State Key Laboratory of Neurobiology and Frontiers Center for Brain Science of Ministry of Education, Fudan University
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- DOD ADNI (Department of Defense) [W81XWH-12-2-0012]
- National Institute on Aging
- AbbVie
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Araclon Biotech
- BioClinica, Inc
- Biogen
- Bristol-Myers Squibb Company
- CereSpir, Inc
- Cogstate
- Genentech, Inc
- Fujirebio
- GE Healthcare
- IXICO Ltd
- Janssen Alzheimer Immunotherapy Research & Development, LLC.
- Johnson & Johnson Pharmaceutical Research & Development LLC.
- Lumosity
- Lundbeck
- Merck Co, Inc
- Meso Scale Diagnostics, LLC.
- NeuroRx Research
- Neurotrack Technologies
- Novartis Pharmaceuticals Corporation
- Pfizer Inc
- Piramal Imaging
- Servier
- Takeda Pharmaceutical Company
- Transition Therapeutics
- Canadian Institutes of Health Research
- French National Foundation on Alzheimer's disease and related disorders
- Labex DISTALZ grant
- Inserm
- Institut Pasteur de Lille
- Universite de Lille 2
- Lille University Hospital
- Medical Research Council [503480]
- Alzheimer's Research UK [503176]
- Wellcome Trust [082604/2/07/Z]
- German Federal Ministry of Education and Research (BMBF): Competence Network Dementia (CND) [01GI0102, 01GI0711, 01GI0420]
- NIH/NIA [R01 AG033193, U01 AG032984, U24 AG021886, U01 AG016976]
- NIA [AG081220]
- AGES [N01-AG-12100]
- NHLBI [R01 HL105756]
- Icelandic Heart Association
- Erasmus Medical Center
- Erasmus University
- Alzheimer's Association grant [ADGC-10-196728]
- National Institute of Biomedical Imaging and Bioengineering
- Eisai Inc
- Elan Pharmaceuticals, Inc
- Eli Lilly and Company
- EuroImmun
- F. Hoffmann-La Roche Ltd
The triggering receptor expressed on myeloid cells 2 (TREM2) gene has been reported to increase the risk of Alzheimer's disease (AD). The soluble TREM2 protein (sTREM2) in cerebrospinal fluid (CSF) was also associated with AD. However, the role of sTREM2 in AD and its genetic modifiers remain unclear. We carried out a genome-wide association study for CSF sTREM2 levels using participants from the Alzheimer's Disease Neuroimaging Initiative and validated the significant association in an independent cohort from Chinese Alzheimer's Biomarker and LifestylE study. rs7232 in membrane spanning 4-domains A6A (MS4A6A) gene was associated with CSF sTREM2 levels at genome-wide significance (p = 1.42 x 10(-15)). The locus influences CSF sTREM2 levels especially in nondemented individuals. And the association was replicable in the validation cohort from Chinese Alzheimer's Biomarker and LifestylE study (p = 0.0106). Besides, the expressions of MS4A6A and TREM2 were correlated in brain regions (p < 2 x 10(-16)). The findings of our study suggest that the AD risk variant in the MS4A6A gene participates in the regulation of sTREM2. (C) 2019 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据