Assessing the causal role of lipid metabolites in Alzheimer's disease: A mendelian randomization study.

IF 7.8 Q2 BUSINESS The Journal of Prevention of Alzheimer's Disease Pub Date : 2025-04-01 Epub Date: 2025-01-23 DOI:10.1016/j.tjpad.2025.100067

Haoxiang Hu, Jiesheng Mao, Yunhan Zhao, Yihan Zhang, Caixiang Zhuang, Jiang Hai He, Xiaokai Yang

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Abstract

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.

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评估脂质代谢物在阿尔茨海默病中的因果作用：亡羊补牢式随机研究

背景：脂质代谢物与阿尔茨海默病（AD）之间的因果关系尚不清楚且相互矛盾。本研究旨在系统评估脂质代谢物与AD之间的因果关系。方法：采用两步双向孟德尔随机化（MR）研究。用于评估因果关系的主要分析技术是逆方差加权（IVW）。此外，还进行了中介分析，以评估脂质体在脂质- ad途径中作为介质的可能功能。结果：在分析的213种脂质代谢物中，与AD有显著因果关系的是大LDL胆固醇酯（L-LDL-CE）（OR = 1.236, 95% CI = 1.052 ~ 1.453, P = 0.010）、大LDL总胆固醇（L-LDL-TC）（OR = 1.506, 95% CI = 1.235 ~ 1.835, P < 0.001）、中LDL总胆固醇（M-LDL-TC）（OR = 1.378, 95% CI = 1.132 ~ 1.677, P = 0.001）。中介分析进一步揭示神经酰胺（d42:2）和磷脂酰肌醇（PI）（18:1_18:1）是这一关系的潜在中介。结论：确定与阿尔茨海默病有因果关系的特定脂质代谢物，为阿尔茨海默病的发病机制提供了新的见解，并突出了预防策略的潜在靶点。

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来源期刊

The Journal of Prevention of Alzheimer's Disease Medicine-Psychiatry and Mental Health

CiteScore

9.20

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0.00%

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期刊介绍： The JPAD Journal of Prevention of Alzheimer’Disease will publish reviews, original research articles and short reports to improve our knowledge in the field of Alzheimer prevention including: neurosciences, biomarkers, imaging, epidemiology, public health, physical cognitive exercise, nutrition, risk and protective factors, drug development, trials design, and heath economic outcomes.JPAD will publish also the meeting abstracts from Clinical Trial on Alzheimer Disease (CTAD) and will be distributed both in paper and online version worldwide.We hope that JPAD with your contribution will play a role in the development of Alzheimer prevention.