biostudies-literatureSu WMthe Science and Technology Bureau Fund of Sichuan Provincethe National Key Research and Development Program of Chinathe National Natural Science Fund of SichuanNational Natural Science Fund of Chinathe 1·3·5 project for disciplines of excellence - Clinical Research Fund, West China Hospital, Sichuan University954-961https://www.ebi.ac.uk/biostudies/studies/S-EPMC10579488biostudies-literatureUnknown94(11)<h4>Background</h4>Alzheimer's disease (AD) is the leading cause of dementia. Currently, there are no effective disease-modifying treatments for AD. Mendelian randomisation (MR) has been widely used to repurpose licensed drugs and discover novel therapeutic targets. Thus, we aimed to identify novel therapeutic targets for AD and analyse their pathophysiological mechanisms and potential side effects.<h4>Methods</h4>A two-sample MR integrating the identified druggable genes was performed to estimate the causal effects of blood and brain druggable expression quantitative trait loci (eQTLs) on AD. A repeat study was conducted using different blood and brain eQTL data sources to validate the identified genes. Using AD markers with available genome-wide association studies data, we evaluated theJournal of neurology, neurosurgery, and psychiatrySystematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer's disease.PMC10579488819711882023YFS02692022YFC27031012022NSFSC07492023HXFH032Jiang ZChen YPSu WMYin KFDou MGu XJDuan QQCai WCWang YCao BfalseSystematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer's disease.<h4>Background</h4>Alzheimer's disease (AD) is the leading cause of dementia. Currently, there are no effective disease-modifying treatments for AD. Mendelian randomisation (MR) has been widely used to repurpose licensed drugs and discover novel therapeutic targets. Thus, we aimed to identify novel therapeutic targets for AD and analyse their pathophysiological mechanisms and potential side effects.<h4>Methods</h4>A two-sample MR integrating the identified druggable genes was performed to estimate the causal effects of blood and brain druggable expression quantitative trait loci (eQTLs) on AD. A repeat study was conducted using different blood and brain eQTL data sources to validate the identified genes. Using AD markers with available genome-wide association studies data, we evaluated the2023-01-01T00:00:00Z2023 Nov2026-06-11T03:20:22.947Z2025-04-19T17:31:56.924ZS-EPMC105794883734909110.1136/jnnp-2023-331142