Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies
| Autor: | Anne Stuendl, Anja Schneider, Niels Kruse, Karin M Danzer, Claudia Bartels, Wiebke Moebius, Brit Mollenhauer, Marcel Kunadt |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology Parkinson's disease animal diseases cerebrospinal fluid [Lewy Body Disease] Cohort Studies chemistry.chemical_compound metabolism [Cerebrospinal Fluid] 0302 clinical medicine Cerebrospinal fluid metabolism [Exosomes] cerebrospinal fluid [Parkinson Disease] Longitudinal Studies Neurodegeneration Parkinson Disease alpha-Synuclein Female extracellular vesicles Lewy Body Disease medicine.medical_specialty metabolism [Parkinson Disease] metabolism [Lewy Body Disease] exosomes Exosome cerebrospinal fluid Progressive supranuclear palsy 03 medical and health sciences Protein Aggregates α-synuclein mental disorders medicine Humans ddc:610 physiology [Protein Aggregates] biosynthesis [alpha-Synuclein] Alpha-synuclein Dementia with Lewy bodies business.industry Original Articles medicine.disease Microvesicles nervous system diseases 030104 developmental biology Cross-Sectional Studies nervous system chemistry Immunology Parkinson’s disease Neurology (clinical) business 030217 neurology & neurosurgery Follow-Up Studies cerebrospinal fluid [alpha-Synuclein] |
| Zdroj: | Brain 139(2), 481-494 (2016). doi:10.1093/brain/awv346 Brain |
| DOI: | 10.1093/brain/awv346 |
| Popis: | Stuendl et al. show that CSF exosomes of patients with Parkinson’s disease or dementia with Lewy bodies contain α-synuclein and induce α-synuclein aggregation in a reporter cell line. Thus, exosomes may support inter-neuronal transmission of α-synuclein pathology. CSF exosomal α-synuclein may serve as a biomarker in α-synuclein-related neurodegeneration. Extracellular α-synuclein has been proposed as a crucial mechanism for induction of pathological aggregate formation in previously healthy cells. In vitro, extracellular α-synuclein is partially associated with exosomal vesicles. Recently, we have provided evidence that exosomal α-synuclein is present in the central nervous system in vivo. We hypothesized that exosomal α-synuclein species from patients with α-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-α-synuclein related disorder that clinically overlaps with Parkinson’s disease, and neurological controls. Cerebrospinal fluid exosome numbers, α-synuclein protein content of cerebrospinal fluid exosomes and their potential to induce oligomerization of α-synuclein were analysed. The quantification of cerebrospinal fluid exosomal α-synuclein showed distinct differences between patients with Parkinson’s disease and dementia with Lewy bodies. In addition, exosomal α-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 α-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 α-synuclein, which could initiate oligomerization of soluble α-synuclein in target cells and confer disease pathology. |
| Databáze: | OpenAIRE |
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