Cellular and Molecular Neurobiology

, Volume 36, Issue 3, pp 437–448 | Cite as

α-Synuclein in Extracellular Vesicles: Functional Implications and Diagnostic Opportunities

  • Camilla Lööv
  • Clemens R. Scherzer
  • Bradley T. Hyman
  • Xandra O. Breakefield
  • Martin Ingelsson
Review Paper

Abstract

Fibrillar inclusions of intraneuronal α-synuclein can be detected in certain brain areas from patients with Parkinson’s disease (PD) and other disorders with Lewy body pathology. These insoluble protein aggregates do not themselves appear to have a prominent neurotoxic effect, whereas various α-synuclein oligomers appear harmful. Although it is incompletely known how the prefibrillar species may be pathogenic, they have been detected both within and on the outside of exosomes and other extracellular vesicles (EVs), suggesting that such structures may mediate toxic α-synuclein propagation between neurons. Vesicular transfer of α-synuclein may thereby contribute to the hierarchical spreading of pathology seen in the PD brain. Although the regulation of α-synuclein release via EVs is not understood, data suggest that it may involve other PD-related molecules, such as LRRK2 and ATP13A2. Moreover, new evidence indicates that CNS-derived EVs in plasma have the potential to serve as biomarkers for diagnostic purposes. In a recent study, levels of α-synuclein were found to be increased in L1CAM-positive vesicles isolated from plasma of PD patients compared to healthy controls, and follow-up studies will reveal whether α-synuclein in EVs could be developed as a future disease biomarker. Preferentially, toxic prefibrillar α-synuclein oligomers should then be targeted as a biomarker—as evidence suggests that they reflect the disease process more closely than total α-synuclein content. In such studies, it will be essential to adopt stringent EV isolation protocols in order to avoid contamination from the abundant pool of free plasma α-synuclein in different aggregational states.

Keywords

Extracellular vesicles Exosomes α-Synuclein 

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Camilla Lööv
    • 1
  • Clemens R. Scherzer
    • 3
  • Bradley T. Hyman
    • 2
  • Xandra O. Breakefield
    • 1
  • Martin Ingelsson
    • 1
    • 4
  1. 1.Departments of Neurology and Radiology, Massachusetts General Hospital and Center for NeuroDiscoveryHarvard Medical SchoolBostonUSA
  2. 2.Departments of Neurology and Radiology, Massachusetts General Hospital and Alzheimer’s Disease Research CenterHarvard Medical SchoolBostonUSA
  3. 3.Neurogenomics Lab and Parkinson Personalized Medicine Program, Harvard Medical SchoolBrigham & Women’s HospitalCambridgeUSA
  4. 4.Department of Public Health, Molecular Geriatrics, Rudbeck LaboratoryUppsala UniversityUppsalaSweden

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