Bridging Integrator 1(BIN1) Genotypes With Alzheimer’s Disease Biomarkers

Background: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.Objective:We explored the effects of BIN1 loci on AD specific biomarkers (CSF proteins, brain structures, glucose and β-amyloid (Aβ) metabolisms) to investigate the role BIN1 in AD pathogenesis.Methods:We calculated the associations of BIN1 loci with CSF and Neuroimaging markers at baseline and follow-up in multiple linear models in 812 ADNI (Alzheimer’s Disease Neuroimaging Initiative) subjects at baseline and follow-up. Furthermore, we analysed their association in CN, MCI and AD subgroup.Results: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 loci were also associated with the glucose metabolism in left temprol (rs3943703:Pc=0.038), right angular (rs1469980:Pc=0.003) and temporal cortex (rs1469980:Pc=0.01, rs3943703: Pc= 0.047) on FDG-PET, but not with Aβ deposition on AV45-PET imaging. BIN1 genotypes were strongly related to atrophy of hippocampus (rs7561528: Pc=0.011), CA1 (rs1469980:Pc=0.029), parahippocampus (rs72838284, Pc=0.017) and amygdala (rs7561528, Pc= 0.022) on MRI. Furthermore, subgroup analysis confirmed these significant findings.Conclusion:This study supported that BIN1 contributes to the risk of AD by altering neural degeneration biomarkers (abnormal CSF tau, brain atrophy and glucose metabolism).