Department of Biochemistry and Molecular Biomedicine, Universitat de Barcelona, Barcelona, Spain.
Institute of Biomedicine of University of Barcelona (IBUB), University of Barcelona (UB), Barcelona, 08028, Spain.
Fluids Barriers CNS. 2023 Dec 4;20(1):90. doi: 10.1186/s12987-023-00494-5.
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.
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.
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.
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.
由于缺乏易于获取且信息量充足的生物标志物，帕金森病（PD）的诊断往往较为滞后，而此时已经有大量多巴胺能神经元消失。视网膜作为中枢神经系统（CNS）中一个长期被忽视的部分，近来受到了关注。人们发现，脑脊液的组成通过微流循环影响房水的组成。此外，在 PD 患者的大脑中发现的改变与视网膜有关。这一新范式强调了房水作为鉴定差异浓缩代谢物样本的潜力，如果这些代谢物也在患者的血液或脑脊液中发生改变，最终可能成为生物标志物。在这项研究中，我们旨在分析健康对照者和 PD 患者房水的组成。
采用靶向代谢组学方法，通过质谱法测定浓度。使用主成分分析和线性判别等统计方法，选择可区分患者和对照者的差异浓缩代谢物。
在这项 PD 患者房水中的首次代谢组学研究中，发现 16 种化合物的水平升高；差异浓缩的分子分为生物胺、氨基酸和酰基肉碱。一种生物胺——腐胺，单独就可以作为一种能够区分 PD 和对照样本的代谢物。代谢物的改变水平存在相关性，表明升高源于涉及精氨酸代谢的共同机制。
腐胺、酪氨酸和肉碱三种代谢物的组合能够正确地将健康参与者与 PD 患者分类。代谢物水平的改变提示精氨酸代谢发生改变。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治疗药物引起的，因为其中一位患者尚未服用左旋多巴，但服用了多巴胺受体激动剂。
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