Altiné-Samey Rayhanatou, Antier Daniel, Mavel Sylvie, Dufour-Rainfray Diane, Balageas Anna-Chloé, Beaufils Emilie, Emond Patrick, Foucault-Fruchard Laura, Chalon Sylvie
UMR 1253, iBrain, Université de Tours, Inserm, Tours, France.
CHU Tours, Service Pharmacie, Tours, France.
Fundam Clin Pharmacol. 2021 Jun;35(3):582-594. doi: 10.1111/fcp.12654. Epub 2021 Mar 8.
Alzheimer's disease (AD) leads to the progressive loss of memory and other cognitive functions. It is the most common form of dementia in the elderly and has become a major public health problem due to the increase in life expectancy. Although the detection of AD is based on several neuropsychological tests, imaging, and biological analyses, none of these biomarkers allows a clear understanding of the pathophysiological mechanisms involved in the disease, and no efficient treatment is currently available. Metabolomics, which allows the study of biochemical alterations underlying pathological processes, could help to identify these mechanisms, to discover new therapeutic targets, and to monitor the therapeutic response and disease progression. In this review, we have summarized and analyzed the results from a number of studies on metabolomics analyses performed in biological samples originated from the central nervous system, in AD subjects, and in animal models of this disease. This synthesis revealed modified expression of specific metabolites in pathological conditions which allowed the identification of significantly impacted metabolic pathways both in animals and humans, such as the arginine biosynthesis and the alanine, aspartate, and glutamate metabolism. We discuss the potential biochemical mechanisms involved, the extent to which they could impact the specific hallmarks of AD, and the therapeutic approaches which could be proposed as a result.
阿尔茨海默病（AD）会导致记忆力和其他认知功能的逐渐丧失。它是老年人中最常见的痴呆形式，由于预期寿命的增加，已成为一个重大的公共卫生问题。尽管AD的检测基于多种神经心理学测试、影像学和生物学分析，但这些生物标志物都无法让人清楚地了解该疾病所涉及的病理生理机制，目前也没有有效的治疗方法。代谢组学能够研究病理过程背后的生化改变，有助于识别这些机制、发现新的治疗靶点，并监测治疗反应和疾病进展。在这篇综述中，我们总结并分析了多项针对源自中枢神经系统的生物样本、AD患者以及该疾病动物模型所进行的代谢组学分析研究结果。这一综合分析揭示了特定代谢物在病理条件下的表达变化，从而能够识别在动物和人类中均受到显著影响的代谢途径，如精氨酸生物合成以及丙氨酸、天冬氨酸和谷氨酸代谢。我们讨论了其中潜在的生化机制、它们对AD特定特征的影响程度，以及由此可能提出的治疗方法。
