Systematic identification of risk factors and drug repurposing options for Alzheimer's disease

Introduction: Several Mendelian randomization studies have been conducted that identified multiple risk factors for Alzheimer's disease (AD). However, they typically focus on a few pre-selected risk factors.

Methods: A two-sample Mendelian randomization (MR) study was used to systematically examine the potential causal associations of 1037 risk factors/medical conditions and 31 drugs with the risk of late-onset AD. To correct for multiple comparisons, the false discovery rate was set at < 0.05.

Results: There was strong evidence of a causal association between glioma risk, reduced trunk fat-free mass, lower education levels, lower intelligence and a higher risk of AD. For 31 investigated treatments (such as antihypertensive drugs), we found limited evidence for their associations.

Discussion: MR found robust evidence of causal associations between glioma, trunk fat-free, and AD. Our study also confirms that higher educational attainment and higher intelligence are associated with a reduced risk of AD.