Abstract
Background and aim: Discriminating multiple system atrophy-parkinsonism (MSA-P) from Parkinson's disease (PD) is challenging. We aimed to provide a new method to make an identification between MSA-P and PD by combining biofluid marker with electrophysiology marker.Methods: The XYCQ EV Enrichment KIT was applied to extract extracellular vesicles (EVs) from saliva. The levels of α-syn which included total α-syn (α- synTotal), phosphorylated-ser129 α-syn (α-synPS129) and oligomeric α-syn (α-synOlig) in EVs of saliva were tested by new developed Electrochemiluminescence (ECL) assays. We collected multi-motor unit potential (MUP) of all participants who conducted external anal sphincter electromyography (EAS-EMG). The duration, phase, amplitude and satellite potential of EAS-EMG were analyzed. The Receiver operator characteristic (ROC) curve was adopted to analyze the diagnostic utility of α-syn in EVs of saliva, EAS-EMG for MSA-P.Results: In EVs of saliva, the α-synTotal concentrations were lower in MSA-P than PD (P = 0.003). No significant difference was shown in α-synOlig and α-synPS129. α-synTotal 4.46 pg/ng distinguished MSA-P from PD with area under the curve (AUC) 0.804. Compared with PD, the duration, phase and satellite potential of EAS-EMG in MSA-P were increased (P = 0.002, 0.008, 0.001). There was no significant difference in amplitude. ROC curve showed that the duration (AUC: 0.780), phase (AUC: 0.751), and satellite potential (AUC: 0.809) had both diagnostic value for MSA-P. The combination of α-synTotal in salivary EVs and EAS-EMG (including duration, phase and satellite potential) could efficiently make a differentiation between MSA-P and PD with sensitivity of 100% and specificity of 86%. The AUC value was 0.901.Conclusion: The study suggested the combination of α-synTotal in salivary EVs and EAS-EMG could help efficiently distinguish MSA-P from PD.
Highlights
Synucleinopathy is one kind of neurodegenerative disease featured by the aggregation of insoluble α-synuclein (α-syn)
No significant difference in age, sex distribution, disease duration, onset age, Unified Parkinson’s Disease Rating Scale (UPDRS)-III, H&Y was indicated between Multiple system atrophy (MSA)-P and Parkinson’s disease (PD)
Our study showed that α-synTotal levels in extracellular vesicles (EVs) of saliva were lower in MSA were Parkinsonian (MSA-P) than PD
Summary
Synucleinopathy is one kind of neurodegenerative disease featured by the aggregation of insoluble α-synuclein (α-syn). These pathological inclusions often deposited in the neurons or in the glia cell [1, 2]. Multiple system atrophy (MSA) is classified as α-synucleinopathy. The main clinical characteristics of MSA included cerebellar ataxia, disorder of autonomic nerve function, poorly levodopa-responsive parkinsonism, and pyramidal symptom [3]. The diagnosis of MSA is principally depended on clinical symptoms, with a high risk of misdiagnosis. MSA-P shares similar neuropathological, cognitive and clinical profiles with PD, complicating its diagnosis. Discriminating multiple system atrophy-parkinsonism (MSA-P) from Parkinson’s disease (PD) is challenging. We aimed to provide a new method to make an identification between MSA-P and PD by combining biofluid marker with electrophysiology marker
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