CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease
文献类型：期刊论文
| 作者 | Zhang DF1,2; Li J3; Wu H2,4; Cui Y3; Bi R1; Zhou HJ1; Wang HZ1; Zhang C5; Wang D1; Kong QP4 |
| 刊名 | NEUROPSYCHOPHARMACOLOGY
 |
| 出版日期 | 2015 |
| 卷号 | 41期号:4页码:1034-1045 |
| 通讯作者 | jiangtz@nlpr.ia.ac.cn ; yaoyg@mail.kiz.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | 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. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02020003) and Sichuan Province (2014JZ0004). The authors declare no conflict of interest. |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/9386]  |
| 专题 | 昆明动物研究所_重大疾病机理的遗传学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 昆明动物研究所_遗传资源与进化国家重点实验室 昆明动物研究所_分子人类学 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 2.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China 3.Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China 4.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming , Chin 5.Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China 6.Mental Health Center and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, China 7.CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China 8.Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China 9.Queensland Brain Institute, University of Queensland, Brisbane, Australia |
| 推荐引用方式 GB/T 7714 | Zhang DF,Li J,Wu H,et al. CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease[J]. NEUROPSYCHOPHARMACOLOGY,2015,41(4):1034-1045. |
| APA | Zhang DF.,Li J.,Wu H.,Cui Y.,Bi R.,...&Yao YG[*].(2015).CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease.NEUROPSYCHOPHARMACOLOGY,41(4),1034-1045. |
| MLA | Zhang DF,et al."CFH Variants Affect Structural and Functional Brain Changes and Genetic Risk of Alzheimer's Disease".NEUROPSYCHOPHARMACOLOGY 41.4(2015):1034-1045. |
入库方式： OAI收割
来源：昆明动物研究所
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