Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Department of Neurology, Qingdao Hospital, University of Health and Rehabilitation Sciences, Qingdao, China.
J Alzheimers Dis. 2024;101(2):693-704. doi: 10.3233/JAD-240372.
Bridging integrator 1 (BIN1) gene polymorphism has been reported to play a role in the pathological processes of Alzheimer's disease (AD).
To explore the association of BIN1 loci with neuroinflammation and AD pathology.
Alzheimer's Disease Neuroimaging Initiative (ADNI, N = 495) was the discovery cohort, and Chinese Alzheimer's Biomarker and LifestylE (CABLE, N = 619) study was used to replicate the results. Two BIN1 gene polymorphism (rs7561528 and rs744373) were included in the analysis. Multiple linear regression model and causal mediation analysis conducted through 10,000 bootstrapped iterations were used to examine the BIN1 loci relationship with cerebrospinal fluid (CSF) AD biomarkers and alternative biomarker of microglial activation microglia-soluble triggering receptor expressed on myeloid cells 2 (sTREM2).
In ADNI database, we found a significant association between BIN1 loci (rs7561528 and rs744373) and levels of CSF phosphorylated-tau (P-tau) (pc = 0.017; 0.010, respectively) and total-tau (T-tau) (pc = 0.011; 0.013, respectively). The BIN1 loci were also correlated with CSF sTREM2 levels (pc = 0.010; 0.008, respectively). Mediation analysis demonstrated that CSF sTREM2 partially mediated the association of BIN1 loci with P-tau (Proportion of rs7561528 : 20.8%; Proportion of rs744373 : 24.8%) and T-tau (Proportion of rs7561528 : 36.5%; Proportion of rs744373 : 43.9%). The analysis in CABLE study replicated the mediation role of rs7561528.
This study demonstrated the correlation between BIN1 loci and CSF AD biomarkers as well as microglia biomarkers. Additionally, the link between BIN1 loci and tau pathology was partially mediated by CSF sTREM2.
桥接整合因子 1（BIN1）基因多态性已被报道在阿尔茨海默病（AD）的病理过程中发挥作用。
探讨 BIN1 基因座与神经炎症和 AD 病理学的关系。
采用阿尔茨海默病神经影像学倡议（ADNI，N=495）作为发现队列，采用中国阿尔茨海默病生物标志物和生活方式（CABLE，N=619）研究进行结果复制。纳入了两个 BIN1 基因多态性（rs7561528 和 rs744373）进行分析。通过 10000 次自举迭代进行多元线性回归模型和因果中介分析，以检验 BIN1 基因座与脑脊液（CSF）AD 生物标志物和小胶质细胞激活的替代生物标志物小胶质细胞可溶性触发受体表达在髓样细胞 2（sTREM2）的关系。
在 ADNI 数据库中，我们发现 BIN1 基因座（rs7561528 和 rs744373）与 CSF 磷酸化 tau（P-tau）（pc=0.017；0.010，分别）和总 tau（T-tau）（pc=0.011；0.013，分别）水平之间存在显著关联。BIN1 基因座也与 CSF sTREM2 水平相关（pc=0.010；0.008，分别）。中介分析表明，CSF sTREM2 部分介导了 BIN1 基因座与 P-tau（rs7561528 的比例：20.8%；rs744373 的比例：24.8%）和 T-tau（rs7561528 的比例：36.5%；rs744373 的比例：43.9%）的关联。CABLE 研究的分析复制了 rs7561528 的中介作用。
本研究表明 BIN1 基因座与 CSF AD 生物标志物以及小胶质细胞生物标志物之间存在相关性。此外，BIN1 基因座与 tau 病理学之间的联系部分由 CSF sTREM2 介导。
