Exploring the Causality Between Plasma Brain-Derived Neurotrophic Factor and Neurological Diseases: A Mendelian...

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Brain-derived neurotrophic factor (BDNF) is a crucial protein in the nervous system.
• The role of BDNF in neurological diseases remains controversial.
• Understanding BDNF's impact is vital for neurodegenerative disease research.

Purpose of the Study:

• To investigate the causal association between plasma BDNF levels and the risk of neurological diseases.
• To utilize Mendelian randomization for robust causal inference.
• To clarify BDNF's role in conditions like Alzheimer's disease and epilepsy.

Main Methods:

• Genome-wide association study (GWAS) on plasma proteins in 3,301 European participants.
• Identification of 25 genetic variations as instrumental variables for BDNF.
• Two-sample Mendelian randomization (MR) analysis with sensitivity and reverse MR analyses.

Main Results:

• A significant causal relationship was confirmed between higher BDNF levels and reduced risk of Alzheimer's disease (AD).
• Higher BDNF levels were also associated with a decreased risk of epilepsy.
• Reverse MR analysis indicated a potential bidirectional relationship between AD and BDNF levels.

Conclusions:

• Elevated plasma BDNF is associated with a lower risk of AD and focal epilepsy.
• BDNF may act as a protective factor against the development of AD and focal epilepsy.
• These findings highlight BDNF's significant role in the pathogenesis of AD and focal epilepsy.