“Reassessing the Inflammatory Hypothesis of Alzheimer’s Disease: A Cross-Replication Mendelian Randomization Analysis of Interleukin Pathways”

Neuroinflammation is increasingly recognized as a key contributor to the pathogenesis of Alzheimer’s disease (AD). Circulating cytokines, particularly interleukins (ILs), play critical roles in immune signaling pathways that regulate neuroinflammatory processes, amyloid plaque formation, and neuronal injury.Observational studies have reported associations between systemic inflammatory markers and AD risk or progression; however, these studies are limited by confounding and reverse causation.To explore the potential causal role of inflammatory pathways, this study aims to systematically evaluate the causal associations between genetically predicted circulating levels of multiple interleukins and the risk of Alzheimer’s disease using a Mendelian randomization (MR) approach.

神经炎症日益被认定为阿尔茨海默病（Alzheimer’s disease, AD）发病机制的关键致病因素。循环细胞因子，尤其是白细胞介素（interleukins, ILs），在调控神经炎症过程、淀粉样斑块形成与神经元损伤的免疫信号通路中发挥关键作用。现有观察性研究已报道全身炎症标志物与AD发病风险或疾病进展之间存在关联，但此类研究受限于混杂偏倚与反向因果问题。为探究炎症通路的潜在因果作用，本研究拟采用孟德尔随机化（Mendelian randomization, MR）方法，系统评估多组白细胞介素的遗传预测循环水平与阿尔茨海默病发病风险之间的因果关联。