PDF(Pubmed)
Abstract：
BACKGROUND: The lack of accessible and informative biomarkers results in a delayed diagnosis of Parkinson\'s disease (PD), whose symptoms appear when a significant number of dopaminergic neurons have already disappeared. The retina, a historically overlooked part of the central nervous system (CNS), has gained recent attention. It has been discovered that the composition of cerebrospinal fluid influences the aqueous humor composition through microfluidic circulation. In addition, alterations found in the brain of patients with PD have a correlate in the retina. This new paradigm highlights the potential of the aqueous humor as a sample for identifying differentially concentrated metabolites that could, eventually, become biomarkers if also found altered in blood or CSF of patients. In this research we aim at analyzing the composition of the aqueous humor from healthy controls and PD patients.
METHODS: A targeted metabolomics approach with concentration determination by mass spectrometry was used. Statistical methods including principal component analysis and linear discriminants were used to select differentially concentrated metabolites that allow distinguishing patients from controls.
RESULTS: In this first metabolomics study in the aqueous humor of PD patients, elevated levels of 16 compounds were found; molecules differentially concentrated grouped into biogenic amines, amino acids, and acylcarnitines. A biogenic amine, putrescine, alone could be a metabolite capable of differentiating between PD and control samples. The altered levels of the metabolites were correlated, suggesting that the elevations stem from a common mechanism involving arginine metabolism.
CONCLUSIONS: A combination of three metabolites, putrescine, tyrosine, and carnitine was able to correctly classify healthy participants from PD patients. Altered metabolite levels suggest altered arginine metabolism. The pattern of metabolomic disturbances was not due to the levodopa-based dopamine replacement medication because one of the patients was not yet taking levodopa but a dopamine receptor agonist.
METHODS: A targeted metabolomics approach with concentration determination by mass spectrometry was used. Statistical methods including principal component analysis and linear discriminants were used to select differentially concentrated metabolites that allow distinguishing patients from controls.
RESULTS: In this first metabolomics study in the aqueous humor of PD patients, elevated levels of 16 compounds were found; molecules differentially concentrated grouped into biogenic amines, amino acids, and acylcarnitines. A biogenic amine, putrescine, alone could be a metabolite capable of differentiating between PD and control samples. The altered levels of the metabolites were correlated, suggesting that the elevations stem from a common mechanism involving arginine metabolism.
CONCLUSIONS: A combination of three metabolites, putrescine, tyrosine, and carnitine was able to correctly classify healthy participants from PD patients. Altered metabolite levels suggest altered arginine metabolism. The pattern of metabolomic disturbances was not due to the levodopa-based dopamine replacement medication because one of the patients was not yet taking levodopa but a dopamine receptor agonist.
摘要：
背景：缺乏可获得的和信息丰富的生物标志物导致帕金森病（PD）的延迟诊断，当大量多巴胺能神经元已经消失时，其症状就会出现。视网膜,中枢神经系统（CNS）的一个历史上被忽视的部分，最近引起了关注。已经发现,脑脊液的组成通过微流体循环影响房水组成。此外,在PD患者的大脑中发现的改变与视网膜有关。这种新的范式突出了房水作为样品的潜力，用于鉴定差异浓缩的代谢物，最终,如果在患者的血液或CSF中也发现改变，则成为生物标志物。在这项研究中，我们旨在分析健康对照和PD患者的房水成分。
方法：使用通过质谱进行浓度测定的靶向代谢组学方法。使用包括主成分分析和线性判别的统计方法来选择差异浓缩的代谢物，以区分患者与对照组。
结果：在PD患者房水的第一个代谢组学研究中，发现了16种化合物的水平升高；不同浓度的分子分为生物胺，氨基酸,和酰基肉碱.一种生物胺，腐胺,单独可以是能够区分PD和对照样品的代谢物。代谢物水平的改变是相关的，这表明升高源于涉及精氨酸代谢的共同机制。
结论：三种代谢物的组合，腐胺,酪氨酸,和肉碱能够正确分类健康参与者从PD患者。代谢物水平的改变表明精氨酸代谢的改变。代谢组学紊乱的模式不是由于基于左旋多巴的多巴胺替代药物，因为其中一名患者尚未服用左旋多巴，而是多巴胺受体激动剂。
方法：使用通过质谱进行浓度测定的靶向代谢组学方法。使用包括主成分分析和线性判别的统计方法来选择差异浓缩的代谢物，以区分患者与对照组。
结果：在PD患者房水的第一个代谢组学研究中，发现了16种化合物的水平升高；不同浓度的分子分为生物胺，氨基酸,和酰基肉碱.一种生物胺，腐胺,单独可以是能够区分PD和对照样品的代谢物。代谢物水平的改变是相关的，这表明升高源于涉及精氨酸代谢的共同机制。
结论：三种代谢物的组合，腐胺,酪氨酸,和肉碱能够正确分类健康参与者从PD患者。代谢物水平的改变表明精氨酸代谢的改变。代谢组学紊乱的模式不是由于基于左旋多巴的多巴胺替代药物，因为其中一名患者尚未服用左旋多巴，而是多巴胺受体激动剂。
