title: Bridging Integrator 1 (BIN1) Genotypes Mediate Alzheimer's Disease Risk by Altering Neuronal Degeneration.
abstract: Bridging integrator 1 (BIN1) has been identified as one of the most associated loci for Alzheimer's disease (AD), and recently was reported to modulate tau pathology to mediate AD in vitro. However, the effects of BIN1 on the AD related biomarkers in AD continuum were not specifically assessed.
  
  
  
  We explored the effects of BIN1 loci on AD specific biomarkers (CSF proteins, brain structures, glucose and amyloid-β (Aβ) metabolisms) to investigate the role BIN1 in AD pathogenesis.
  
  
  
  We calculated the associations of BIN1 loci with these markers at baseline and follow-up in multiple linear models in 812 ADNI subjects.
  
  
  
  BIN1 loci were significantly associated with the levels of T-tau (rs744373: pc = 0.047, rs13031703: pc = 0.042) and P-tau (rs744373: pc = 0.044, rs13031703: pc = 0.019), but not with Aβ in CSF test. BIN1 genotypes were strongly related to atrophy of hippocampus (rs7561528: pc = 0.011), CA1 (rs1469980: pc = 0.029) and parahippocampus (rs72838284, pc = 0.017) on MRI, and to glucose metabolism on FDG-PET, but not to Aβ deposition on AV45-PET imaging. Furthermore, haplotype and subgroup analysis confirmed these significant findings. In addition, the loci associated with these markers were also identified to influence the risk for AD in the meta-analysis of 74 046 European individuals.
  
  
  
  This study supported that BIN1 contributes to the risk of AD by altering neural degeneration (abnormal tau, brain atrophy and glucose metabolism) but not Aβ pathology.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, China.
authors.forename: Hui-Fu
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Hao
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, China.
authors.forename: Xi-Chen
authors.initials: XC
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Nanjing First Hospital, Nanjing Medical University, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China.
authors.forename: Meng-Shan
authors.initials: MS
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Computer Science and Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.
authors.forename: Dao-Qiang
authors.initials: DQ
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, China.|Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China.|Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, China.|Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, China.
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009410:Nerve Degeneration / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; C101410:BIN1 protein, human; D015415:Biomarkers; C054369:MAPT protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D016875:tau Proteins; D005947:Glucose
keywords: Alzheimer’s disease; Aβ deposition; BIN1; brain structure; cerebrospinal fluid; glucose metabolism