α‐Synuclein in oligodendroglia and neuron‐derived blood exosomes distinguishes between synucleinopathies

AbstractBackgroundSynucleinopathies are neurodegenerative diseases characterized by aggregation and deposition of α‐synuclein in different brain cells. Diagnosis of these neurological disorders is very challenging due to overlapping complex clinical symptoms. Developing reliable biomarkers that can distinguish among the synucleinopathies is an urgent public health need. Recently, α‐synuclein was shown to transfer via exosomes between different brain cells suggesting that measuring α‐synuclein in specific brain cell‐derived exosomes could serve as a potential biomarker for synucleinopathies.MethodIn this study, we used antibody‐coated magnetic dynabeads to immunochemically enrich specific exosomes released by neurons or oligodendrocytes from serum of healthy individuals and patients with Parkinson’s disease (PD) and Multiple System Atrophy (MSA) and measured biomarker concentration in them by a sensitive electro‐chemiluminescence ELISA. CNS exosomes were isolated from serum/plasma from a discovery cohort and a validation cohort containing 50 patients with MSA, 50 patients with PD and 50 healthy controls in each cohorts.ResultSignificantly higher concentrations of α‐synuclein were observed in both neuronal and oligodendroglial exosomes from patients than in controls. The absolute values of α‐synuclein in neuronal and oligodendroglial exosomes provided moderate separation between the MSA and PD groups, yet the ratio between the two cell types derived exosomal α‐synuclein allowed separating the two disease groups with 90.0% sensitivity and specificity.Conclusionα‐Synuclein in CNS‐derived blood exosomes provides a sensitive biomarker for distinguishing these two synucleinopathies using a blood test and suggest that the method can be expanded further for other neurodegenerative diseases.