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α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease.
Neurosci Lett. 2019 03 23; 696:114-120.NL

Abstract

BACKGROUND

Detection of α-synuclein (α-syn) in biological fluids such as saliva may serve as potential biomarker of PD. α-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 α-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 α-syn levels, including total α-syn (α-synTotal), oligomeric α-syn (α-synOlig) and phosphorylated-ser129 α-syn (α-synPS129), were measured by Electrochemiluminescence (ECL) assays. Diagnostic value and clinical relevance of salivary EVs α-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 α-synOlig and α-synOlig/α-synTotal 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 α-synTotal、α-synPS129、 α-synPS129/α-synTotal ratio between PD and HCs (P = 0.723, 0.634, 0.734, respectively). α-synOlig 2.05 pg/ng distinguished PD from HCs with sensitivity 92% and specificity 86%; α-synOlig /α-synTotal 0.18 pg/ng differentiated PD from HCs with sensitivity 81% and specificity 71%. No significant correlation between salivary EVs α-synOlig, α-synOlig/α-synTotal and disease severity was found.

CONCLUSIONS

Exosomes are present in PD saliva. The α-synOlig and α-synOlig/α-synTotal ratio in salivary EVs may serve as potential diagnostic biomarkers for PD.

Authors+Show Affiliations

Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.Clinical Laboratory, Peking University Third Hospital, Peking University, Beijing, China; Department of Pathology, Peking University School of Basic Medical Sciences, Peking University, Beijing, China; Beijing Key Laboratory of Research and Transformation on Neurodegenerative Diseases Biomarkers, Beijing, China.Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China.Center for Neurodegenerative Disease, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Parkinson's Disease Center, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China. Electronic address: bxbkyjs@sina.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30579996

Citation

Cao, Zhentang, et al. "Α-Synuclein in Salivary Extracellular Vesicles as a Potential Biomarker of Parkinson's Disease." Neuroscience Letters, vol. 696, 2019, pp. 114-120.
Cao Z, Wu Y, Liu G, et al. Α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease. Neurosci Lett. 2019;696:114-120.
Cao, Z., Wu, Y., Liu, G., Jiang, Y., Wang, X., Wang, Z., & Feng, T. (2019). Α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease. Neuroscience Letters, 696, 114-120. https://doi.org/10.1016/j.neulet.2018.12.030
Cao Z, et al. Α-Synuclein in Salivary Extracellular Vesicles as a Potential Biomarker of Parkinson's Disease. Neurosci Lett. 2019 03 23;696:114-120. PubMed PMID: 30579996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - α-Synuclein in salivary extracellular vesicles as a potential biomarker of Parkinson's disease. AU - Cao,Zhentang, AU - Wu,Yufeng, AU - Liu,Genliang, AU - Jiang,Ying, AU - Wang,Xuemei, AU - Wang,Zhan, AU - Feng,Tao, Y1 - 2018/12/21/ PY - 2018/10/18/received PY - 2018/12/19/revised PY - 2018/12/19/accepted PY - 2018/12/24/pubmed PY - 2019/9/3/medline PY - 2018/12/24/entrez KW - Biomarker KW - Extracellular vesicles KW - Oligomeric α-synuclein KW - Parkinson's disease KW - Saliva SP - 114 EP - 120 JF - Neuroscience letters JO - Neurosci Lett VL - 696 N2 - BACKGROUND: Detection of α-synuclein (α-syn) in biological fluids such as saliva may serve as potential biomarker of PD. α-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 α-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 α-syn levels, including total α-syn (α-synTotal), oligomeric α-syn (α-synOlig) and phosphorylated-ser129 α-syn (α-synPS129), were measured by Electrochemiluminescence (ECL) assays. Diagnostic value and clinical relevance of salivary EVs α-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 α-synOlig and α-synOlig/α-synTotal 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 α-synTotal、α-synPS129、 α-synPS129/α-synTotal ratio between PD and HCs (P = 0.723, 0.634, 0.734, respectively). α-synOlig 2.05 pg/ng distinguished PD from HCs with sensitivity 92% and specificity 86%; α-synOlig /α-synTotal 0.18 pg/ng differentiated PD from HCs with sensitivity 81% and specificity 71%. No significant correlation between salivary EVs α-synOlig, α-synOlig/α-synTotal and disease severity was found. CONCLUSIONS: Exosomes are present in PD saliva. The α-synOlig and α-synOlig/α-synTotal ratio in salivary EVs may serve as potential diagnostic biomarkers for PD. SN - 1872-7972 UR - https://www.unboundmedicine.com/medline/citation/30579996/α_Synuclein_in_salivary_extracellular_vesicles_as_a_potential_biomarker_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(18)30875-9 DB - PRIME DP - Unbound Medicine ER -