Mendelian Randomization Identified CHRNE as a Potential Drug Target for Alzheimer’s disease

Abstract

Abstract Since clinical trials of novel therapeutics for Alzheimer’s disease (AD) have been largely disappointing, drug repurposing may provide an effective approach to identifying therapeutics to treat AD. In this study, two-sample Mendelian randomization analysis was employed to evaluate brain and blood transcriptomic data for 1263 actionable proteins targeted by approved drugs or in the clinical phase of drug development. The genome-wide association studies included 17008 patients with AD and 37154 controls to predict the potential target gene for AD. CHRNE (Cholinergic Receptor Nicotinic Epsilon Subunit) mRNA expression increased the risk for AD in both the brain and the blood. Bayesian colocalization analysis confirmed that this was not coincidentally due to linkage disequilibrium. Furthermore, the proteins encoded by CHRNE were mainly expressed on the surface of microglia. The trials of drugs targeting CHRNE should be prioritized to design future functional studies and therapy for AD.