Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Monash University, Melbourne, VIC, 3800, Australia.
Nat Commun. 2020 Nov 10;11(1):5698. doi: 10.1038/s41467-020-19473-7.
Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer's disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM gangliosides) and lipid classes previously associated with cardiometabolic disease (phosphatidylethanolamine and triglycerides). We subsequently identified similar lipid signatures in both cohorts with future disease. Lastly, we developed multivariate lipid models that improved classification and prediction. Our results provide a holistic view between the lipidome and AD using a comprehensive approach, providing targets for further mechanistic investigation.
脂质代谢的变化与阿尔茨海默病（AD）的发病和病理密切相关。脂质是由许多同分异构和等压的物质组成的复杂分子，需要进行详细的分析才能解释其生物学意义。我们扩展的靶向脂质组学平台（32 类 569 种物质）可以实现详细的脂质分离和特征描述。在这项研究中，我们检查了两个队列（AIBL，n=1112 和 ADNI，n=800）的外周样本。我们能够识别出与从包括醚脂质、鞘脂（特别是 GM 神经节苷脂）和以前与心血管代谢疾病相关的脂质类（磷脂酰乙醇胺和甘油三酯）的脂质途径相关的、与普遍存在的 AD 相关的一致性外周特征。我们随后在两个队列中都发现了具有未来疾病的类似脂质特征。最后，我们开发了多变量脂质模型，提高了分类和预测能力。我们的研究结果使用综合方法提供了脂质组学与 AD 之间的整体视图，为进一步的机制研究提供了目标。
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