engStuendl, AnneKunadt, MarcelKruse, NielsBartels, ClaudiaMoebius, WiebkeDanzer, Karin MMollenhauer, BritSchneider, AnjaInduction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies.info:eu-repo/classification/ddc/610Cerebrospinal Fluid: metabolismCohort StudiesCross-Sectional StudiesExosomes: metabolismFemaleFollow-Up StudiesHumansLewy Body Disease: cerebrospinal fluidLewy Body Disease: metabolismLongitudinal StudiesMaleParkinson Disease: cerebrospinal fluidParkinson Disease: metabolismProtein Aggregates: physiologyalpha-Synuclein: biosynthesisalpha-Synuclein: cerebrospinal fluidProtein Aggregatesalpha-SynucleinExtracellular 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.Brain 139(2), 481-494 (2016). doi:10.1093/brain/awv346info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionOxford Univ. Press2016info:eu-repo/semantics/openAccessDEhttps://pub.dzne.de/record/138377https://pub.dzne.de/search?p=id:%22DZNE-2020-04699%22Researchersinfo:eu-repo/semantics/altIdentifier/doi/10.1093/brain/awv346info:eu-repo/semantics/altIdentifier/issn/0006-8950info:eu-repo/semantics/altIdentifier/pmid/pmid:26647156info:eu-repo/semantics/altIdentifier/issn/1460-2156