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Cited by 676Parkinson's Disease Mechanisms and TreatmentsExtracellular vesicles in diseaseNeuroinflammation and Neurodegeneration Mechanisms

Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson’s disease

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Shi, Min, Liu, Changqin, Cook, Travis J., Bullock, Kristin M., Zhao, Yanchun, Ginghina, Carmen, Li, Yanfei, Aro, Patrick +10 more·2014·Acta Neuropathologica
DOI 10.1007/s00401-014-1314-yPMC PMC4201967
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Abstract

Extracellular α-synuclein is important in the pathogenesis of Parkinson's disease (PD) and also as a potential biomarker when tested in the cerebrospinal fluid (CSF). The performance of blood plasma or serum α-synuclein as a biomarker has been found to be inconsistent and generally ineffective, largely due to the contribution of peripherally derived α-synuclein. In this study, we discovered, via an intracerebroventricular injection of radiolabeled α-synuclein into mouse brain, that CSF α-synuclein was readily transported to blood, with a small portion being contained in exosomes that are relatively specific to the central nervous system (CNS). Consequently, we developed a technique to evaluate the levels of α-synuclein in these exosomes in individual plasma samples. When applied to a large cohort of clinical samples (267 PD, 215 controls), we found that in contrast to CSF α-synuclein concentrations, which are consistently reported to be lower in PD patients compared to controls, the levels of plasma exosomal α-synuclein were substantially higher in PD patients, suggesting an increased efflux of the protein to the peripheral blood of these patients. Furthermore, although no association was observed between plasma exosomal and CSF α-synuclein, a significant correlation between plasma exosomal α-synuclein and disease severity (r = 0.176, p = 0.004) was observed, and the diagnostic sensitivity and specificity achieved by plasma exosomal α-synuclein were comparable to those determined by CSF α-synuclein. Further studies are clearly needed to elucidate the mechanism involved in the transport of CNS α-synuclein to the periphery, which may lead to a more convenient and robust assessment of PD clinically.

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  • Plasma exosomal alpha-synuclein levels are markedly higher in Parkinson's disease patients and correlate with disease severity.

    “Additionally, plasma exosomal 𝛂 -syn levels are markedly higher in PD patients and correlate with disease severity (532).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [532]

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Authors
Shi, M., Liu, C., Cook, T. J., Bullock, K. M., Zhao, Y., Ginghina, C., Li, Y., Aro, P., Dator, R., He, C., Hipp, M. J., Zabetian, C. P., Peskind, E. R., Hu, S.-C., Quinn, J. F., Galasko, D. R., Banks, W. A., & Zhang, J.
Affiliations
  • University of Washington (US)
  • First Affiliated Hospital of Xiamen University (CN)
  • Oregon Health & Science University (US)
  • University of California San Diego (US)
Corresponding author
Zhang, Jing
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2014-07-06
Volume
128
Issue
5
Pages
639-650
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-014-1314-y
PMC
PMC4201967
OpenAlex
W1985458075
Cited by
676
References
10
Citations by year
2026: 49 · 2025: 62 · 2024: 88 · 2023: 74 · 2022: 80 · 2021: 72 · 2020: 72 · 2019: 63 · 2018: 36 · 2017: 32 · 2016: 30 · 2015: 15 · 2014: 3
FWCI
17.39
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institute on Aging (R01AG033398, P50AG005131, P50 AG003156-30, P50AG005136)
  • National Institute of Neurological Disorders and Stroke (U01NS082137, P50NS062684, R01NS065070, P50 NS062684-6221, R01NS057567, R21NS085425)
  • National Institute of Environmental Health Sciences (P30ES007033-6364, R01ES019277, P42ES004696, R01ES016873, P42 ES004696-5897, P30ES007033, T32ES015459)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Parkinson's disease, alpha-synuclein, exosomes, plasma biomarkers, cerebrospinal fluid, intracerebroventricular administration, disease severity, sensitivity and specificity
MeSH terms
Adult, Aged, Aged, 80 and over, Animals, Brain, Female, Humans, Male, Microscopy, Electron, Middle Aged, Parkinson Disease, ROC Curve, Mass Spectrometry, Cohort Studies, Case-Control Studies, Neural Cell Adhesion Molecule L1, Mice, alpha-Synuclein, Exosomes

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