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 | |
发表期刊 | NEUROPSYCHOPHARMACOLOGY |
2016-03-01 | |
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 |
DOI | 10.1038/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 | |
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 |
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 |
推荐引用方式 GB/T 7714 | 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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