journal articles
ASSESSING THE CAUSAL ROLE OF LIPID METABOLITES IN ALZHEIMER\'S DISEASE: A MENDELIAN RANDOMIZATION STUDY
Haoxiang Hu, Jiesheng Mao, Yunhan Zhao, Yihan Zhang, Yihan Zhang, Jiang hai He, Xiaokai Yang
BACKGROUND: The causal relationship between lipid metabolites and Alzheimer's disease (AD) remains unclear and contradictory. This study aimed to systematically assess the causal relationship between lipid metabolites and AD.
METHODS: A two-step bidirectional Mendelian Randomization (MR) study was employed. The principal analytical technique used to evaluate causation was inverse variance weighting (IVW). Furthermore, mediation analysis was conducted to evaluate the possible function of lipidomes as mediators in the lipid-AD pathway.
RESULTS: Among the 213 lipid metabolites analyzed, significant causal associations with AD were identified Cholesterol esters in large LDL(L-LDL-CE) (OR = 1.236, 95 %CI = 1.052–1.453, P = 0.010), Total cholesterol in large LDL(L-LDL-TC) (OR = 1.506, 95 %CI = 1.235–1.835, P < 0.001), Total cholesterol in medium LDL(M-LDL-TC) (OR = 1.378, 95 %CI = 1.132–1.677, P = 0.001). Mediation analysis further revealed ceramide (d42:2) and phosphatidylinositol (PI) (18:1_18:1) as potential mediators in this relationship.
CONCLUSION: The identification of specific lipid metabolites with causal effects on AD provides new insights into AD pathogenesis and highlights potential targets for preventive strategies.
CITATION:
Haoxiang Hu ; Jiesheng Mao ; Yunhan Zhao ; Yihan Zhang ; Caixiang Zhuang ; Jiang hai He ; Xiaokai Yang (2025): Assessing the causal role of lipid metabolites in Alzheimer's disease: A mendelian randomization study. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2025.10006