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CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease
Zhang, Deng-Feng1,2; Li, Jin3,4; Wu, Huan2,5; Cui, Yue3,4; Bi, Rui1; Zhou, He-Jiang1; Wang, Hui-Zhen1; Zhang, Chen6; Wang, Dong1; Kong, Qing-Peng5; Li, Tao7,8; Fang, Yiru6; Jiang, Tianzi3,4,9,10,11; Yao, Yong-Gang1,2,9; ADNI
2016-03-01
发表期刊NEUROPSYCHOPHARMACOLOGY
卷号41期号:4页码:1034-1045
文章类型Article
摘要The immune response is highly active in Alzheimer's disease (AD). Identification of genetic risk contributed by immune genes to AD may provide essential insight for the prognosis, diagnosis, and treatment of this neurodegenerative disease. In this study, we performed a genetic screening for AD-related top immune genes identified in Europeans in a Chinese cohort, followed by a multiple-stage study focusing on Complement Factor H (CFH) gene. Effects of the risk SNPs on AD-related neuroimaging endophenotypes were evaluated through magnetic resonance imaging scan, and the effects on AD cerebrospinal fluid biomarkers (CSF) and CFH expression changes were measured in aged and AD brain tissues and AD cellular models. Our results showed that the AD-associated top immune genes reported in Europeans (CR1, CD33, CLU, and TREML2) have weak effects in Chinese, whereas CFH showed strong effects. In particular, rs1061170 (P-meta = 5.0 x 10(-4)) and rs800292 (P-meta = 1.3 x 10(-5)) showed robust associations with AD, which were confirmed in multiple world-wide sample sets (4317 cases and 16 795 controls). Rs1061170 (P = 2.5 x 10(-3)) and rs800292 (P = 4.7 x 10(-4)) risk-allele carriers have an increased entorhinal thickness in their young age and a higher atrophy rate as the disease progresses. Rs800292 risk-allele carriers have higher CSF tau and A beta levels and severe cognitive decline. CFH expression level, which was affected by the risk-alleles, was increased in AD brains and cellular models. These comprehensive analyses suggested that CFH is an important immune factor in AD and affects multiple pathological changes in early life and during disease progress.
WOS标题词Science & Technology ; Life Sciences & Biomedicine
DOI10.1038/npp.2015.232
关键词[WOS]FACTOR HY402H POLYMORPHISM ; MACULAR DEGENERATION ; FACTOR-H ; COGNITIVE IMPAIRMENT ; ALTERNATIVE PATHWAY ; AMYLOID PLAQUES ; COMPLEMENT ; ASSOCIATION ; HIPPOCAMPAL ; INFLAMMATION
收录类别SCI
语种英语
项目资助者Strategic Priority Research Program (B) of the Chinese Academy of Sciences(XDB02020003) ; Sichuan Province(2014JZ0004)
WOS研究方向Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
WOS类目Neurosciences ; Pharmacology & Pharmacy ; Psychiatry
WOS记录号WOS:000369786900012
引用统计
被引频次:17[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ia.ac.cn/handle/173211/10842
专题脑网络组研究中心
作者单位1.Chinese Acad Sci, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming 650204, Peoples R China
2.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming, Peoples R China
3.Chinese Acad Sci, Brainnetome Ctr, Beijing 100190, Peoples R China
4.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China
5.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Peoples R China
6.Shanghai Jiao Tong Univ, Sch Med, Shanghai Mental Hlth Ctr, Div Mood Disorders, Shanghai 200030, Peoples R China
7.Sichuan Univ, Mental Hlth Ctr, Chengdu 610064, Peoples R China
8.Sichuan Univ, West China Hosp, Psychiat Lab, Chengdu 610064, Peoples R China
9.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China
10.Univ Elect Sci & Technol China, Sch Life Sci & Technol, Minist Educ, Key Lab NeuroInformat, Chengdu 610054, Peoples R China
11.Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia
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Zhang, Deng-Feng,Li, Jin,Wu, Huan,et al. CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease[J]. NEUROPSYCHOPHARMACOLOGY,2016,41(4):1034-1045.
APA Zhang, Deng-Feng.,Li, Jin.,Wu, Huan.,Cui, Yue.,Bi, Rui.,...&ADNI.(2016).CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.NEUROPSYCHOPHARMACOLOGY,41(4),1034-1045.
MLA Zhang, Deng-Feng,et al."CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease".NEUROPSYCHOPHARMACOLOGY 41.4(2016):1034-1045.
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