Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, Lørenskog, Norway.
CNS Neurosci Ther. 2024 Apr;30(4):e14532. doi: 10.1111/cns.14532. Epub 2023 Nov 21.
Despite extensive work to identify diagnostic plasma markers for Parkinson's disease (PD), there are still no accepted and validated surrogate biomarkers. Mitophagy-associated proteins (MAPs), including PTEN-induced putative kinase 1 (PINK1), Parkin, phosphoglycerate mutase 5 (PGAM5), BCL2 interacting protein 3 (BNIP3), and phosphorylated-TBK1 (p-TBK1), are, to our best knowledge, not well studied as a panel of biomarkers of neurodegeneration in PD.
The study population comprised 116 age-matched controls (HC), 179 PD patients, alongside and 90 PD syndromes (PDs) divided between two cohorts: (i) the modeling cohort (cohort 1), including 150 PD, 97 HC, and 80 PDs; and (ii) the validated cohort (cohort 2), including 29 PD, 19 HC, and 10 PDs.
MAPs are elevated in the plasma of PD patients. PINK1, Parkin, and PGAM5 displayed the top three measurable increase trends in amplitude compared to BNIP3 and p-TBK1. Moreover, the area under the curve (AUC) values of PINK1, PGAM5, and Parkin were ranked the top three MAP candidates in diagnosis accuracy for PD from HC, but the MAPs make it hard to differentiate PD from PDs. In addition, there are higher plasma PINK1-Parkin levels and prominent diagnostic accuracy in A-synuclein (+) subjects than in A-synuclein (-) subjects.
These results uncover that plasma MAPs (PINK1, Parkin, and PGAM5) may be potentially useful diagnostic biomarkers for PD diagnosis. Studies on larger cohorts would be required to test whether elevated plasma MAP levels are related to PD risk or prognosis.
尽管已经开展了大量工作来鉴定帕金森病（PD）的诊断性血浆标志物，但仍没有被接受和验证的替代生物标志物。在我们的认知范围内，线粒体自噬相关蛋白（MAPs），包括 PTEN 诱导的假定激酶 1（PINK1）、Parkin、磷酸甘油酸变位酶 5（PGAM5）、BCL2 相互作用蛋白 3（BNIP3）和磷酸化-TBK1（p-TBK1），尚未作为 PD 神经退行性变的生物标志物进行深入研究。
研究人群包括 116 名年龄匹配的对照组（HC）、179 名 PD 患者和 90 名 PD 综合征（PDs），分为两个队列：（i）建模队列（队列 1），包括 150 名 PD、97 名 HC 和 80 名 PDs；（ii）验证队列（队列 2），包括 29 名 PD、19 名 HC 和 10 名 PDs。
PD 患者的血浆中 MAPs 升高。与 BNIP3 和 p-TBK1 相比，PINK1、Parkin 和 PGAM5 的振幅增加趋势最高。此外，PINK1、PGAM5 和 Parkin 的曲线下面积（AUC）值在 PD 与 HC 之间的诊断准确性方面排名前三位，但 MAPs 使得难以区分 PD 与 PDs。此外，A-synuclein（+）患者的血浆 PINK1-Parkin 水平较高，诊断准确性较高，而 A-synuclein（-）患者则较低。
这些结果表明，血浆 MAPs（PINK1、Parkin 和 PGAM5）可能是 PD 诊断的潜在有用的诊断生物标志物。需要对更大的队列进行研究，以测试升高的血浆 MAP 水平是否与 PD 风险或预后有关。
