Department of Hygienic Toxicology, School of Public Health, Harbin Medical University, 157 Baojian Road, NanGang District, Harbin, 150081, Heilongjiang Province, People's Republic of China.
Mol Neurobiol. 2024 Dec;61(12):10216-10226. doi: 10.1007/s12035-024-04197-2. Epub 2024 May 6.
The objective of the study is to determine the causal relationship and potential mechanisms between Parkinson's disease (PD) and neuroinflammatory and neurotoxic mediators. We conducted two-sample Mendelian randomization (2SMR) study and multivariable Mendelian randomization (MVMR) analysis to investigate the causality between PD and neuroinflammatory and neurotoxic mediators. The mediation analysis with MR was also conducted to determine the potential mediating effect of neuroinflammatory and neurotoxic mediators between asthma and PD. Genetically predicted levels of nine neuroinflammation were associated with changes in PD risk. The associations of PD with CCL24, galectin-3 levels, haptoglobin, and Holo-Transcobalamin-2 remained significant in multivariable analyses. The mediation analysis with MR revealed that asthma affects PD through CCL24 and galectin-3. The results showed neuroinflammation could affect the pathogenesis of PD. In the combined analysis of these nine variables, CCL24, galectin-3 levels, HP, and Holo-Transcobalamin-2 alone were found to be significant. Asthma plays an intermediary role through CCL24 and galectin-3 levels.
本研究旨在确定帕金森病（PD）与神经炎症和神经毒性介质之间的因果关系和潜在机制。我们进行了两样本 Mendelian 随机化（2SMR）研究和多变量 Mendelian 随机化（MVMR）分析，以调查 PD 与神经炎症和神经毒性介质之间的因果关系。还进行了中介分析，以确定神经炎症和神经毒性介质在哮喘和 PD 之间的潜在中介作用。9 种神经炎症的遗传预测水平与 PD 风险的变化相关。在多变量分析中，CCL24、半乳糖凝集素-3 水平、触珠蛋白和全转钴胺素-2 与 PD 的关联仍然显著。MR 中介分析表明，哮喘通过 CCL24 和半乳糖凝集素-3 影响 PD。结果表明，神经炎症可能影响 PD 的发病机制。在对这 9 个变量的联合分析中，仅 CCL24、半乳糖凝集素-3 水平、HP 和全转钴胺素-2 具有统计学意义。哮喘通过 CCL24 和半乳糖凝集素-3 水平发挥中介作用。
