Erythrocytic α-Synuclein as a potential biomarker for Parkinson's disease.
Electrochemiluminescence
Erythrocyte
Parkinson’s disease
α-Synuclein
Journal
Translational neurodegeneration
ISSN: 2047-9158
Titre abrégé: Transl Neurodegener
Pays: England
ID NLM: 101591861
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
01
2019
accepted:
24
04
2019
entrez:
25
5
2019
pubmed:
28
5
2019
medline:
28
5
2019
Statut:
epublish
Résumé
Erythrocytes are a major source of peripheral α-synuclein (α-Syn). The goal of the current investigation is to evaluate erythrocytic total, oligomeric/aggregated, and phosphorylated α-Syn species as biomarkers of Parkinson's disease (PD). PD and healthy control blood samples were collected along with extensive clinical history to determine whether total, phosphorylated, or aggregated α-Syn derived from erythrocytes (the major source of blood α-Syn) are more promising and consistent biomarkers for PD than are free α-Syn species in serum or plasma. Using newly developed electrochemiluminescence assays, concentrations of erythrocytic total, aggregated and phosphorylated at Ser129 (pS129) α-Syn, separated into membrane and cytosolic components, were measured in 225 PD patients and 133 healthy controls and analyzed with extensive clinical measures. The total and aggregated α-Syn levels were significantly higher in the membrane fraction of PD patients compared to healthy controls, but without alterations in the cytosolic component. The pS129 level was remarkably higher in PD subjects than in controls in the cytosolic fraction, and to a lesser extent, higher in the membrane fraction. Combining age, erythrocytic membrane aggregated α-Syn, and cytosolic pS129 levels, a model generated by using logistic regression analysis was able to discriminate patients with PD from neurologically normal controls, with a sensitivity and a specificity of 72 and 68%, respectively. These results suggest that total, aggregated and phosphorylated α-Syn levels are altered in PD erythrocytes and peripheral erythrocytic α-Syn is a potential PD biomarker that needs further validation.
Sections du résumé
BACKGROUND
BACKGROUND
Erythrocytes are a major source of peripheral α-synuclein (α-Syn). The goal of the current investigation is to evaluate erythrocytic total, oligomeric/aggregated, and phosphorylated α-Syn species as biomarkers of Parkinson's disease (PD). PD and healthy control blood samples were collected along with extensive clinical history to determine whether total, phosphorylated, or aggregated α-Syn derived from erythrocytes (the major source of blood α-Syn) are more promising and consistent biomarkers for PD than are free α-Syn species in serum or plasma.
METHODS
METHODS
Using newly developed electrochemiluminescence assays, concentrations of erythrocytic total, aggregated and phosphorylated at Ser129 (pS129) α-Syn, separated into membrane and cytosolic components, were measured in 225 PD patients and 133 healthy controls and analyzed with extensive clinical measures.
RESULTS
RESULTS
The total and aggregated α-Syn levels were significantly higher in the membrane fraction of PD patients compared to healthy controls, but without alterations in the cytosolic component. The pS129 level was remarkably higher in PD subjects than in controls in the cytosolic fraction, and to a lesser extent, higher in the membrane fraction. Combining age, erythrocytic membrane aggregated α-Syn, and cytosolic pS129 levels, a model generated by using logistic regression analysis was able to discriminate patients with PD from neurologically normal controls, with a sensitivity and a specificity of 72 and 68%, respectively.
CONCLUSIONS
CONCLUSIONS
These results suggest that total, aggregated and phosphorylated α-Syn levels are altered in PD erythrocytes and peripheral erythrocytic α-Syn is a potential PD biomarker that needs further validation.
Identifiants
pubmed: 31123587
doi: 10.1186/s40035-019-0155-y
pii: 155
pmc: PMC6521422
doi:
Types de publication
Journal Article
Langues
eng
Pagination
15Subventions
Organisme : NINDS NIH HHS
ID : U01 NS091272
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS104511
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS082137
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH118160
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG056711
Pays : United States
Déclaration de conflit d'intérêts
The ethics approval and study protocol were approved by the Institutional Review Boards of Peking University, Peking University Third Hospital, Beijing, China. Written consent was obtained from all subjects.Not applicable.The authors declare that they have no competing interests.
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