D3Validation, Fondazione Istituto Italiano di Tecnologia, via Morego 30, 16163, Genoa, Italy.
Scuola Superiore Sant'Anna, via Piazza Martiri della Libertà, 33, 56127, Pisa, Italy.
Metabolomics. 2019 May 3;15(5):74. doi: 10.1007/s11306-019-1536-z.
Current markers of Parkinson's disease (PD) fail to detect the early progression of disease state. Conversely, current omics techniques allow the investigation of hundreds of molecules potentially altered by disease conditions. Based on evidence previously collected by our group in a mouse model of PD, we speculated that a particular set of circulating lipids might be significantly altered by the pathology.
The aim of current study was to evaluate the potential of a particular set of N-acyl-phosphatidylethanolamines (NAPEs) as potential non-invasive plasma markers of ongoing neurodegeneration from Parkinson's disease in human subjects.
A panel of seven NAPEs were quantified by LC-MS/MS in the plasma of 587 individuals (healthy controls, n = 319; Parkinson's disease, n = 268); Random Forest classification and statistical modeling was applied to compare Parkinson's disease versus controls. All p-values obtained in different tests were corrected for multiplicity by controlling the false discovery rate (FDR).
The results indicate that this panel of NAPEs is able to distinguish female PD patients from the corresponding healthy controls. Further to this, the observed downregulation of these NAPEs is in line with the results in plasma of a mouse model of Parkinson's (6-OHDA).
In the current study we have shown the downregulation of NAPEs in plasma of PD patients and we thus speculate that these lipids might serve as candidate biomarkers for PD. We also suggest a molecular mechanism, explaining our findings, which involves gut microbiota.
目前的帕金森病(PD)标志物无法检测到疾病状态的早期进展。相反,目前的组学技术允许研究数百种可能因疾病状况而改变的分子。基于我们小组在 PD 小鼠模型中收集的先前证据,我们推测一组特定的循环脂质可能会因病理而发生显著改变。
本研究旨在评估一组特定的 N-酰基-磷脂乙醇胺(NAPEs)作为潜在的非侵入性血浆标志物的潜力,以评估其在人类帕金森病患者中持续神经退行性变的潜力。
通过 LC-MS/MS 在 587 个人的血浆中定量了一组 7 种 NAPEs(健康对照组,n = 319;帕金森病组,n = 268);随机森林分类和统计模型用于比较帕金森病与对照组。在不同的测试中获得的所有 p 值都通过控制假发现率(FDR)来校正多重性。
结果表明,该 NAPEs 组能够区分女性 PD 患者与相应的健康对照者。此外,这些 NAPEs 的下调与帕金森小鼠模型(6-OHDA)血浆中的结果一致。
在目前的研究中,我们已经显示了 PD 患者血浆中 NAPEs 的下调,因此我们推测这些脂质可能作为 PD 的候选生物标志物。我们还提出了一种分子机制,解释了我们的发现,该机制涉及肠道微生物群。