Metabolomics and Analytics Centre, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
Division of Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University, 2333 CC Leiden, The Netherlands.
Int J Mol Sci. 2023 Mar 4;24(5):4960. doi: 10.3390/ijms24054960.
Alzheimer's disease (AD) is an aging-related neurodegenerative disease, leading to the progressive loss of memory and other cognitive functions. As there is still no cure for AD, the growth in the number of susceptible individuals represents a major emerging threat to public health. Currently, the pathogenesis and etiology of AD remain poorly understood, while no efficient treatments are available to slow down the degenerative effects of AD. Metabolomics allows the study of biochemical alterations in pathological processes which may be involved in AD progression and to discover new therapeutic targets. In this review, we summarized and analyzed the results from studies on metabolomics analysis performed in biological samples of AD subjects and AD animal models. Then this information was analyzed by using MetaboAnalyst to find the disturbed pathways among different sample types in human and animal models at different disease stages. We discuss the underlying biochemical mechanisms involved, and the extent to which they could impact the specific hallmarks of AD. Then we identify gaps and challenges and provide recommendations for future metabolomics approaches to better understand AD pathogenesis.
阿尔茨海默病（AD）是一种与衰老相关的神经退行性疾病，导致记忆和其他认知功能的进行性丧失。由于目前尚无治愈 AD 的方法，易患个体人数的增加对公共健康构成了重大新威胁。目前，AD 的发病机制和病因仍不清楚，也没有有效的治疗方法来减缓 AD 的退行性影响。代谢组学可以研究病理过程中的生化变化，这些变化可能与 AD 的进展有关，并发现新的治疗靶点。在这篇综述中，我们总结和分析了在 AD 患者和 AD 动物模型的生物样本中进行的代谢组学分析研究的结果。然后，使用 MetaboAnalyst 对这些信息进行分析，以找到不同疾病阶段的人类和动物模型中不同样本类型之间的失调途径。我们讨论了所涉及的潜在生化机制，以及它们在多大程度上可能影响 AD 的特定特征。然后，我们确定了差距和挑战，并为未来的代谢组学方法提供了建议，以更好地了解 AD 的发病机制。
