Affiliations: [a]
Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China
| [b] Chongqing Key Laboratory of Ageing and Brain Diseases, Chongqing, China
| [c]
Department of Neurology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, China
| [d]
Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China
| [e]
Institute of Brain and Intelligence, Third Military Medical University, Chongqing, China
| [f] State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing, China
| [g]
Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
Correspondence:
[*]
Correspondence to: Drs. Wang-Shen Jin and Yan-Jiang Wang, Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital, Third Military Medical University, Chongqing, China. E-mailsskjws123@163.com (Jin), yanjiang_wang@tmmu.edu.cn (Wang).
Abstract: Background:Abnormal intracellular expression and aggregation of α-synuclein (α-syn) is the histopathological hallmark of several neurodegenerative diseases especially Parkinson’s disease. However, safe and efficient approaches to clear α-syn remain unavailable. Objective:This study aimed to investigate the process of peripheral catabolism of brain-derived α-syn. Methods:Thirty patients with atrioventricular reentrant tachycardia (AVRT) (left accessory pathways) who underwent radiofrequency catheter ablation (RFCA) were enrolled in this study. Blood was collected via catheters from superior vena cava (SVC), inferior vena cava (IVC) proximal to the hepatic vein (HV), the right femoral vein (FV), and femoral artery (FA) simultaneously during RFCA. Plasma α-syn levels of AVRT patients and soluble α-syn levels of the brain samples were measured using enzyme-linked immunosorbent assay kits. Results:The α-syn concentrations in different locations of veins were divided by time-matched arterial α-syn concentrations to generate the venous/arterial (V/A) ratio. The V/A ratio of α-syn from the SVC was 1.204 (1.069–1.339, 95% CI), while the V/A ratio of α-syn from IVC was 0.831 (0.734–0.928, 95% CI), suggesting that brain-derived α-syn in the arterial blood was physiologically cleared while going through the peripheral organs and tissues. And it was estimated that about half of brain soluble α-syn could efflux and be cleared in the periphery. Moreover, the glomerular filtration rate was found correlated with V-A difference (FA-ICV) (p = 0.0272). Conclusion:Under physiological conditions, brain-derived α-syn could efflux into and be catabolized by the peripheral system. The kidney may play a potential role in the clearance of α-syn.
