Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, Suzhou, China.
School of Nursing, Suzhou Medical College of Soochow University, Suzhou, China.
Curr Neurovasc Res. 2024;20(5):553-559. doi: 10.2174/0115672026281995231227070637.
High brain-derived neurotrophic factor (BDNF) concentrations have been found to be associated with a decreased risk of Alzheimer's disease (AD) in observational studies, but the causality for this association remains unclear. Therefore, we aimed to examine the association between genetically determined plasma BDNF levels and AD using a two-sample Mendelian randomization (MR) method.
Twenty single-nucleotide polymorphisms associated with plasma BDNF concentrations were identified as genetic instruments based on a genome-wide association study with 3301 European individuals. Summary-level data on AD were obtained from the International Genomics of Alzheimer's Project, involving 21,982 AD cases and 41,944 controls of European ancestry. To evaluate the relationship between plasma BDNF concentrations and AD, we employed the inverse-variance weighted method along with a series of sensitivity analyses.
The inverse-variance weighted MR analysis showed that genetically determined BDNF concentrations were associated with a decreased risk of AD (odds ratio per SD increase, 0.91; 95% confidence interval, 0.86-0.96; p =0.001). The association between plasma BDNF concentrations and AD was further confirmed through sensitivity analyses using different MR methods, and MR-Egger regression suggested no directional pleiotropy for this association.
Genetically determined BDNF levels were associated with a decreased risk of AD, suggesting that BDNF was implicated in the development of AD and might be a promising target for the prevention of AD.
在观察性研究中发现，大脑源性神经营养因子（BDNF）浓度较高与阿尔茨海默病（AD）的风险降低有关，但这种关联的因果关系尚不清楚。因此，我们旨在使用两样本 Mendelian 随机化（MR）方法，检查遗传决定的血浆 BDNF 水平与 AD 之间的关联。
根据一项涉及 3301 名欧洲人的全基因组关联研究，确定了 20 个与血浆 BDNF 浓度相关的单核苷酸多态性作为遗传工具。AD 的汇总水平数据来自国际阿尔茨海默病基因组学项目，涉及 21982 例 AD 病例和 41944 例欧洲血统对照。为了评估血浆 BDNF 浓度与 AD 之间的关系，我们采用了逆方差加权法以及一系列敏感性分析。
逆方差加权 MR 分析表明，遗传决定的 BDNF 浓度与 AD 的风险降低相关（每增加一个标准差的比值比，0.91；95%置信区间，0.86-0.96；p=0.001）。通过使用不同的 MR 方法进行敏感性分析，进一步证实了血浆 BDNF 浓度与 AD 之间的关联，MR-Egger 回归表明这种关联没有方向性的偏倚。
遗传决定的 BDNF 水平与 AD 的风险降低有关，这表明 BDNF 参与了 AD 的发展，可能是预防 AD 的有前途的靶点。
