title: Neprilysin Confers Genetic Susceptibility to Alzheimer's Disease in Han Chinese.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease, with increasing incidence all over the world. Amyloid-β (Aβ) was considered to be the original cause to AD, and many reported pathogenic or risk genes for AD were located in the Aβ generation and degradation pathways. Neprilysin (NEP), insulin-degrading enzyme (IDE), and matrix metalloprotease-9 (MMP-9) are the most important Aβ-degrading proteases. Accumulating genetic evidence suggested that single nucleotide polymorphisms (SNPs) of these genes confer susceptibility to AD in Caucasian populations. In this study, we screened eight SNPs within these three Aβ-degrading protease genes in 1475 individuals of two independent Han Chinese case-control cohorts. SNP rs1816558 of NEP was found to be significantly associated with AD after adjustment for ε4 allele of the apolipoprotein E gene (APOEε4) and the Bonferroni correction. The remaining variants were not associated with risk of AD in Han Chinese sample set. Further data mining revealed that messenger RNA (mRNA) level of NEP substantially increased during the development of AD and was positively correlated with APP expression. The combined results indicated that NEP confers genetic susceptibility to AD in Han Chinese populations.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Bi
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China.
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Li
authors.affiliation: The Mental Health Center & Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610064, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Ma
authors.affiliation: Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
authors.forename: Yiru
authors.initials: Y
authors.lastname: Fang
authors.affiliation: The Mental Health Center & Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, 610064, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200030, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, 650223, China. yaoyg@mail.kiz.ac.cn.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, 650204, China. yaoyg@mail.kiz.ac.cn.|CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China. yaoyg@mail.kiz.ac.cn.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Yao
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D057225:Data Mining / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015260:Neprilysin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D054730:Protein Interaction Domains and Motifs / Q000235:genetics
chemical_list: D015260:Neprilysin
keywords: Alzheimer’s disease; Aβ-degrading enzyme; Chinese; Genetic susceptibility; Neprilysin