17 Stuendl, Anne Kunadt, Marcel Kruse, Niels Bartels, Claudia Moebius, Wiebke Danzer, Karin M Mollenhauer, Brit Schneider, Anja AG Schneider Göttingen Brain Brain Oxford Univ. Press Oxford 0006-8950 10.1093/brain/awv346 English 481-494 2 139 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. PUB:(DE-HGF)16, ; 0, ; Cerebrospinal Fluid: metabolism Cohort Studies Cross-Sectional Studies Exosomes: metabolism Female Follow-Up Studies Humans Lewy Body Disease: cerebrospinal fluid Lewy Body Disease: metabolism Longitudinal Studies Male Parkinson Disease: cerebrospinal fluid Parkinson Disease: metabolism Protein Aggregates: physiology alpha-Synuclein: biosynthesis alpha-Synuclein: cerebrospinal fluid Protein Aggregates alpha-Synuclein Journal Article 2016 DZNE-2020-04699 2016 pmc:PMC4805087 pmid:26647156 https://pub.dzne.de/record/138377 https://doi.org/10.1093/brain/awv346