The class
Mendelian randomization links CETP inhibition and elevated LDL cholesterol to Lewy body dementia risk (Prog Neuropsychopharmacol Biol Psychiatry 2025)
Original title: Genetic insights of lipid metabolism and lipid-lowering drugs with Lewy body dementia risk: Evidence from Mendelian randomization
To investigate the role of lipid traits and lipid-lowering drug targets in Lewy body dementia, the second most common dementia with unclear mechanisms, researchers performed univariable and multivariable Mendelian randomization on lipid traits, followed by drug-target Mendelian randomization and subtype analysis for lipid-lowering therapies. Genetically predicted LDL cholesterol and remnant cholesterol levels were both associated with increased Lewy body dementia risk, with mediation analysis suggesting an interaction between the two in influencing risk. Drug-target Mendelian randomization identified significant associations between genetically proxied inhibition of ANGPTL3, CETP and HMGCR and Lewy body dementia risk, leading the authors to propose these three targets as potential therapeutic strategies for prevention or treatment of the disease.
Original abstract
Background: Lewy body dementia (LBD) is the second common dementia, with unclear mechanisms and limited treatment options. Dyslipidemia has been implicated in LBD, but the role of lipid-lowering drugs remains underexplored. This study aims to investigate the association between lipid traits, drug targets, and LBD risk using Mendelian Randomization (MR) analysis.
Methods: We performed univariable and multivariable MR analyses to evaluate the causal effects of lipid traits on the risk of LBD. Then, drug-target MR analysis and subtype analysis were conducted to evaluate the effects of lipid-lowering therapies on LBD.
Results: In univariable MR, genetically predicted low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) levels were associated with an increased risk of LBD. Mediation analysis suggested a potential interaction between LDL-C and RC in influencing LBD risk. Drug-target MR analysis identified significant associations between genetically proxied inhibition of ANGPTL3, CETP, and HMGCR and LBD risk.
Conclusion: This MR analysis provided evidence that elevated LDL-C and RC may increase the risk of LBD. Additionally, targeting ANGPTL3, CETP, and HMGCR may represent potential therapeutic strategies for the prevention or treatment of LBD.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.