Prognostic biomarkers of Parkinson's disease in the Spanish EPIC cohort: a multiplatform metabolomics approach.
Prognostic biomarkers of Parkinson's disease in the Spanish EPIC cohort: a multiplatform metabolomics approach.
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DOI：
10.1038/s41531-021-00216-4
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发表时间：
2021-08-16
期刊：
影响因子：
--
通讯作者：
Amiano P
中科院分区：
文献类型：
--
作者：
Gonzalez-Riano C;Saiz J;Barbas C;Bergareche A;Huerta JM;Ardanaz E;Konjevod M;Mondragon E;Erro ME;Chirlaque MD;Abilleira E;Goñi-Irigoyen F;Amiano P
对帕金森病（PD）发病和进展的认识不足，阻碍了其早期诊断和治疗。代谢组学可能揭示PD印记，寻求更广泛的观点，这种疾病在早期和症状前阶段诱导的生化重塑，并揭示潜在的生物标志物。为了实现这一目标，我们利用欧洲营养与癌症前瞻性研究（EPIC）队列的巨大潜力，应用代谢组学寻找早期诊断PD标志物。该队列由健康志愿者组成，随访约15年，直至2011年6月，以确定PD事件。对于这项基于代谢组学的非靶向研究，使用多平台方法分析了39名随机选择的PD（PD前组）和相应对照组个体的基线临床前血浆样本。对数据进行了统计分析，并暴露了33种代谢物水平的变化，包括PD受试者临床前样本中游离脂肪酸（FFA）水平显著降低。然后通过采用靶向HPLC-QqQ-MS方法验证这些结果。在整合所有受影响的代谢物后，我们的发现揭示了早在PD标志发展之前，FFA代谢、线粒体功能障碍、氧化应激和肠-脑轴失调的改变。虽然这些事件的生物学目的仍然未知，但这项工作中强调的重塑代谢途径可能被认为是早期前驱PD的有价值的预后生物标志物。这项工作所揭示的结果具有不可估量的价值，因为这是第一次对疾病发展前多年收集的样本进行研究。
The lack of knowledge about the onset and progression of Parkinson’s disease (PD) hampers its early diagnosis and treatment. Metabolomics might shed light on the PD imprint seeking a broader view of the biochemical remodeling induced by this disease in an early and pre-symptomatic stage and unveiling potential biomarkers. To achieve this goal, we took advantage of the great potential of the European Prospective Study on Nutrition and Cancer (EPIC) cohort to apply metabolomics searching for early diagnostic PD markers. This cohort consisted of healthy volunteers that were followed for around 15 years until June 2011 to ascertain incident PD. For this untargeted metabolomics-based study, baseline preclinical plasma samples of 39 randomly selected individuals that developed PD (Pre-PD group) and the corresponding control group were analyzed using a multiplatform approach. Data were statistically analyzed and exposed alterations in 33 metabolites levels, including significantly lower levels of free fatty acids (FFAs) in the preclinical samples from PD subjects. These results were then validated by adopting a targeted HPLC-QqQ-MS approach. After integrating all the metabolites affected, our finding revealed alterations in FFAs metabolism, mitochondrial dysfunction, oxidative stress, and gut–brain axis dysregulation long before the development of PD hallmarks. Although the biological purpose of these events is still unknown, the remodeled metabolic pathways highlighted in this work might be considered worthy prognostic biomarkers of early prodromal PD. The findings revealed by this work are of inestimable value since this is the first study conducted with samples collected many years before the disease development.
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影响因子：
4.3
作者：
Emamzadeh FN;Surguchov A
通讯作者：
Surguchov A
DOI：
10.1590/s1135-57272004000200004
发表时间：
2004-04-01
期刊：
Revista Española de Salud Pública
影响因子：
--
作者：
González, Carlos A.;Navarro, Carmen;Berenguer, Antonio
通讯作者：
Berenguer, Antonio
影响因子：
11
作者：
Hatano, Taku;Saiki, Shinji;Hattori, Nobutaka
通讯作者：
Hattori, Nobutaka
影响因子：
2.9
作者：
Golovko, MY;Faergeman, NJ;Murphy, EJ
通讯作者：
Murphy, EJ
影响因子：
14.5
作者：
Bogdanov, Mikhail;Matson, Wayne R.;Beal, M. Flint
通讯作者：
Beal, M. Flint