Bridging Integrator 1 (BIN1) Genotypes Mediate Alzheimer's Disease Risk by Altering Neuronal Degeneration

• Published in: Journal of Alzheimer's disease Vol. 52; no. 1; p. 179
• Main Authors: Wang, Hui-Fu, Wan, Yu, Hao, Xiao-Ke, Cao, Lei, Zhu, Xi-Chen, Jiang, Teng, Tan, Meng-Shan, Tan, Lin, Zhang, Dao-Qiang, Tan, Lan, Yu, Jin-Tai
• Format: Journal Article
• Language: English
• Published: Netherlands 26.04.2016
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Amyloid beta-Peptides - cerebrospinal fluid; Biomarkers - metabolism; Brain - diagnostic imaging; Brain - metabolism; Databases, Factual; European Continental Ancestry Group - genetics; Female; Follow-Up Studies; Genetic Predisposition to Disease; Glucose - metabolism; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Degeneration - diagnostic imaging; Nerve Degeneration - genetics; Nerve Degeneration - metabolism; Nuclear Proteins - genetics; Polymorphism, Single Nucleotide; Positron-Emission Tomography; Risk; tau Proteins - cerebrospinal fluid; Tumor Suppressor Proteins - genetics; Aβ deposition; Alzheimer’s disease; BIN1; brain structure; glucose metabolism; cerebrospinal fluid
• DOI: 10.3233/JAD-150972

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.