Title:Association between Plasma Brain-derived Neurotrophic Factor Level and Alzheimer’s Disease: A Mendelian Randomization Study
Volume: 20
Issue: 5
Author(s): Jiaxing You, Yinan Wang, Xinyue Chang, Yi Liu, Yu He, Xiya Zhou, Jinyan Zou, Meng Xiao, Mengyao Shi, Daoxia Guo, Ouxi Shen and Zhengbao Zhu*
Affiliation:
- 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
Keywords:
Brain-derived neurotrophic factor, Alzheimer’s disease, mendelian randomization, neurodegeneration, neuroprotection, amyloid β.
Abstract: Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
