Induction of alpha-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies
2016 | journal article. A publication with affiliation to the University of Göttingen.
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Induction of alpha-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies
Stuendl, A.; Kunadt, M.; Kruse, N.; Bartels, C.; Möbius, W. ; Danzer, K. M. & Mollenhauer, B. et al. (2016)
Brain, 139 pp. 481-494. DOI: https://doi.org/10.1093/brain/awv346
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Details
- Authors
- Stuendl, Anne; Kunadt, Marcel; Kruse, Niels; Bartels, Claudia; Möbius, Wiebke ; Danzer, Karin M.; Mollenhauer, Brit; Schneider, Anja
- Abstract
- Extracellular alpha-synuclein has been proposed as a crucial mechanism for induction of pathological aggregate formation in previously healthy cells. In vitro, extracellular alpha-synuclein is partially associated with exosomal vesicles. Recently, we have provided evidence that exosomal alpha-synuclein is present in the central nervous system in vivo. We hypothesized that exosomal alpha-synuclein species from patients with alpha-synuclein related neurodegeneration serve as carriers for interneuronal disease transmission. We isolated exosomes from cerebrospinal fluid from patients with Parkinson's disease, dementia with Lewy bodies, progressive supranuclear palsy as a non-alpha-synuclein related disorder that clinically overlaps with Parkinson's disease, and neurological controls. Cerebrospinal fluid exosome numbers, alpha-synuclein protein content of cerebrospinal fluid exosomes and their potential to induce oligomerization of alpha-synuclein were analysed. The quantification of cerebrospinal fluid exosomal alpha-synuclein showed distinct differences between patients with Parkinson's disease and dementia with Lewy bodies. In addition, exosomal alpha-synuclein levels correlated with the severity of cognitive impairment in cross-sectional samples from patients with dementia with Lewy bodies. Importantly, cerebrospinal fluid exosomes derived from Parkinson's disease and dementia with Lewy bodies induce oligomerization of alpha-synuclein in a reporter cell line in a dose-dependent manner. Our data suggest that cerebrospinal fluid exosomes from patients with Parkinson's disease and dementia with Lewy bodies contain a pathogenic species of alpha-synuclein, which could initiate oligomerization of soluble alpha-synuclein in target cells and confer disease pathology.
- Issue Date
- 2016
- Status
- published
- Publisher
- Oxford Univ Press
- Journal
- Brain
- ISSN
- 1460-2156; 0006-8950