Objective: Here, we aimed to determine if measuring of α-synuclein concentration in these vesicles from oligodendrocytes and neurons can distinguish between patients with MSA or PD from healthy controls and between MSA and PD patients.

Background: Synucleinopathies are a group of neurodegenerative diseases characterized by aggregation and deposition of α-synuclein (α-syn) in different brain cells. Diagnosis of different synucleinopathies is challenging due to overlapping complex clinical phenotypes. Till date the clinical diagnosis of these disorders are typically made upon physical observations of motor symptoms. However, the overlapping symptoms, at an early stage, often leads to misdiagnosis. Therefore, reliable biomarkers to identify and distinguish different synucleinopathies is an urgent public health need. Exosomes are nano vesicles shed by most cells, carrying cell- and cell-state specific biomolecules, thus provides a rich source of biomarkers. Recently, α-synuclein was shown to transfer from cell to cell via exosomes suggesting that measuring α-synuclein in different brain cell-derived exosomes could serve as a potential window to monitor brain pathologic processes.

Method: Totalserumexosomes from50 healthy individuals, 30 patients with MSA and 50 patients with PD were isolated, and enrichment of neuronal and oligodendroglial exosomes was achieved by selective immunoprecipitation (IP). Capture of exosomes on beads following IP was determined using FACS, western blotting and Tunable Resistive Pulse Sensing (TRPS) analysis. Highly sensitive electrochemiluminescence ELISA was used to measure α-Synuclein concentration.

Results: High concentrations of α-synuclein was detected in exosomes from patients with MSA and PD than in healthy controls. The α-synuclein concentration in oligodendroglial and neuronal exosomes separated MSA and PD groups moderately but the ratio between oligodendroglial and neuronal exosomal α-synuclein separated the two disease groups with 90.0% sensitivity and specificity.

Conclusion: Measurement of α-Synuclein in oligodendroglia and neuron-derived blood exosomes could be a sensitive biomarker for distinguishing patients with MSA from healthy controls and from patients with PD and the method can be further extended to other neurodegenerative diseases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/analysis-of-brain-derived-blood-exosomes-for-diagnostics-of-synucleinopathies/