机构:[a]Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China重点科室诊疗科室神经病学中心神经病学中心首都医科大学附属天坛医院[b]China National Clinical Research Center for Neurological Diseases, Beijing, China[c]Clinical Laboratory, Peking University Third Hospital, Peking University, Beijing, China[d]Department of Pathology, Peking University School of Basic Medical Sciences, Peking University, Beijing, China[e]Beijing Key Laboratory of Research and Transformation on Neurodegenerative Diseases Biomarkers, Beijing, China[f]Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China
Background: Detection of alpha-synuclein (alpha-syn) in biological fluids such as saliva may serve as potential biomarker of PD. alpha-syn pertaining to extracellular vesicles (EVs) has been recently studied in plasma, but not in other biological fluids such as saliva. Aim 1) To investigate the presence of exosomes in PD saliva; 2) to explore the value of alpha-syn in salivary EVs as potential biomarker in PD. Methods: Saliva samples were obtained from 74 PD and 60 healthy controls (HCs). The EVs were extracted from saliva by XYCQ EV Enrichment KIT. Western blot and Nanosight 300 were used to validate the existence of exosomes in EVs and to analyze the size of salivary EVs. Salivary EVs alpha-syn levels, including total alpha-syn (alpha-syn(Total)), oligomeric alpha-syn (alpha-syn(Olig)) and phosphorylated-ser129 alpha-syn (alpha-syn(PS129)), were measured by Electrochemiluminescence (ECL) assays. Diagnostic value and clinical relevance of salivary EVs alpha-syn were assessed by Receiver Operator Characteristic (ROC) curve and Spearman correlation. Results: Alix and CD9 positive EVs, representing the presence of exosomes, was detected in PD salivary samples. Size of salivary EVs was about 30-400 nm. The levels of alpha-syn(Olig) and alpha-syn(Olig)/alpha-syn(Total) in the salivary EVs were higher in PD than in HCs (10.39 +/- 1.46 pg/ng vs.1.37 +/- 0.24 pg/ng, p < 0.001;1.70 +/- 0.52 pg/ng vs.0.67 +/- 0.26 pg/ng, p < 0.001). There was no significant difference in alpha-syn(Total), alpha-syn(PS129), alpha-syn(PS129)/alpha-syn(Total) ratio between PD and HCs (P = 0.723, 0.634, 0.734, respectively). alpha-syn(Olig), 2.05 pg/ng distinguished PD from HCs with sensitivity 92% and specificity 86%; alpha-syn(Olig)/alpha-syn(Total) 0.18 pg/ng differentiated PD from HCs with sensitivity 81% and specificity 71%. No significant correlation between salivary EVs alpha-syn(Olig), alpha-syn(Olig)/asyn(Total) and disease severity was found. Conclusions: Exosomes are present in PD saliva. The alpha-syn(Olig) and alpha-syn(Olig)/alpha-syn(Total) ratio in salivary EVs may serve as potential diagnostic biomarkers for PD.
基金:
National Key R&D Program of the Ministry of Science and Technology of PRC [2016YFC1306501]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81571226, 81771367, 31600724]; Beijing Municipal Science & Technology CommissionBeijing Municipal Science & Technology Commission [Z171100001017041]
第一作者机构:[a]Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[b]China National Clinical Research Center for Neurological Diseases, Beijing, China
通讯作者:
通讯机构:[a]Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China[b]China National Clinical Research Center for Neurological Diseases, Beijing, China[f]Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China[*1]Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 6 Tian Tan Xi Li Street, 100050, Beijing, China.
推荐引用方式(GB/T 7714):
Cao Zhentang,Wu Yufeng,Liu Genliang,et al.alpha-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease[J].NEUROSCIENCE LETTERS.2019,696:114-120.doi:10.1016/j.neulet.2018.12.030.
APA:
Cao, Zhentang,Wu, Yufeng,Liu, Genliang,Jiang, Ying,Wang, Xuemei...&Feng, Tao.(2019).alpha-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease.NEUROSCIENCE LETTERS,696,
MLA:
Cao, Zhentang,et al."alpha-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease".NEUROSCIENCE LETTERS 696.(2019):114-120