Detection of elevated levels of PINK1 in plasma from patients with idiopathic Parkinson's disease

Xianchai Hong; Yi Zheng; Jialong Hou; Tao Jiang; Yao Lu; Wenwen Wang; Shuoting Zhou; Qianqian Ye; Chenglong Xie; Jia Li

doi:10.3389/fnagi.2024.1369014

Detection of elevated levels of PINK1 in plasma from patients with idiopathic Parkinson's disease

Front Aging Neurosci. 2024 Apr 22:16:1369014. doi: 10.3389/fnagi.2024.1369014. eCollection 2024.

Authors

Xianchai Hong^#¹, Yi Zheng^#², Jialong Hou², Tao Jiang², Yao Lu^{2

3}, Wenwen Wang⁴, Shuoting Zhou², Qianqian Ye², Chenglong Xie^{2

5

6

7}, Jia Li²

Affiliations

¹ Department of Neurology Nursing Unit 362 Ward, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ Department of Neurology, Yuhuan City People's Hospital, Taizhou, China.
⁴ The Center of Traditional Chinese Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
⁵ Key Laboratory of Alzheimer's Disease of Zhejiang Province, Wenzhou City, China.
⁶ Institute of Aging, Wenzhou Medical University, Wenzhou, Zhejiang, China.
⁷ Oujiang Laboratory, Wenzhou, Zhejiang, China.

^# Contributed equally.

Abstract

Backgrounds: Numerous lines of evidence support the intricate interplay between Parkinson's disease (PD) and the PINK1-dependent mitophagy process. This study aimed to evaluate differences in plasma PINK1 levels among idiopathic PD, PD syndromes (PDs), and healthy controls.

Methods: A total of 354 participants were included, consisting of 197 PD patients, 50 PDs patients, and 107 healthy controls were divided into two cohorts, namely the modeling cohort (cohort 1) and the validated cohort (cohort 2). An enzyme-linked immunosorbent assay (ELISA)-based analysis was performed on PINK1 and α-synuclein oligomer (Asy-no). The utilization of the area under the curve (AUC) within the receiver-operating characteristic (ROC) curves served as a robust and comprehensive approach to evaluate and quantify the predictive efficacy of plasma biomarkers alone, as well as combined models, in distinguishing PD patients from controls.

Results: PINK1 and Asy-no were elevated in the plasma of PD and PDs patients compared to healthy controls. The AUCs of PINK1 (0.771) and Asy-no (0.787) were supposed to be potentially eligible plasma biomarkers differentiating PD from controls but could not differentiate PD from PDs. Notably, the PINK + Asy-no + Clinical RBD model showed the highest performance in the modeling cohort and was comparable with the PINK1 + Clinical RBD in the validation cohort. Moreover, there is no significant correlation between PINK1 and UPDRS, MMSE, HAMD, HAMA, RBDQ-HK, and ADL scores.

Conclusion: These findings suggest that elevated PINK1 in plasma holds the potential to serve as a non-invasive tool for distinguishing PD patients from controls. Moreover, the outcomes of our investigation lend support to the plausibility of implementing a feasible blood test in future clinical translation.

Keywords: PINK1; Parkinson’s disease; biomarkers; mitophagy; α-synuclein oligomer.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Projects of the National Science Foundation of China (Nos. 81600977 and 82271469) and the Projects of the Natural Science Foundation of Zhejiang Province (LQ23H090007, Y19H090059, and LZ23H090001), and the Projects of the Wenzhou City Committee of Science and Technology (No. Y20220164).