Dopaminergic nigrostriatal denervation and widespread intracellular α-synuclein accumulation are neuropathologic hallmarks of Parkinson’s disease (PD). A constellation of peripheral processes, including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi-marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age-matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables organized in multi-block datasets. The SO-CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)-1β, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP-1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as biomarkers for PD as well as unveil new targets for interventions.

多巴胺能黑质纹状体去神经和广泛的细胞内α-突触核蛋白积聚是帕金森氏病（PD）的神经病理学标志。包括代谢和炎症变化在内的周围过程的星座被认为有助于神经退行性变。在本研究中，我们试图通过应用多标记物发现方法来了解PD的多方面病理生理学。作为帕金森病（EXPAND）研究中外来体的一部分，纳入了50位70岁以上的老年人，20位具有PD的对照和30位年龄相匹配的对照。分析了68种炎症，神经发生和神经可塑性以及氨基酸代谢的循环介质。生物标记的选择是通过顺序和正交协方差选择（SO-CovSel）完成的，一种多平台回归方法，用于处理在多块数据集中组织的高度相关的变量。用七个生物分子构建了具有最佳预测能力，使用最少变量的SO-CovSel模型。该模型允许对94.2±3.1％的PD和100％对照的参与者进行正确分类。患有PD的成年人的生物标志物特征是由白细胞介素（IL）8，巨噬细胞炎性蛋白（MIP）-1β，磷酸乙醇胺和脯氨酸的较高循环水平以及瓜氨酸，IL9和MIP-1α的较低浓度确定的。我们的创新方法可以识别和评估老年人PD的一系列潜在生物标记物的分类性能。