138377 20240826163725.0 10.1093/brain/awv346 doi pmid:26647156 pmid pmc:PMC4805087 pmc 0006-8950 ISSN 1460-2156 ISSN altmetric:4852819 altmetric DZNE-2020-04699 English 610 Stuendl, Anne P:(DE-HGF)0 0 Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies. Oxford 2016 Oxford Univ. Press online Crossref Oxford University Press (OUP) 2015-12-08 print Crossref Oxford University Press (OUP) 2016-02-01 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1724675667_21453 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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. 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 0 Dataset connected to CrossRef, PubMed, Protein Aggregates NLM Chemicals alpha-Synuclein NLM Chemicals Cerebrospinal Fluid: metabolism MeSH Cohort Studies MeSH Cross-Sectional Studies MeSH Exosomes: metabolism MeSH Female MeSH Follow-Up Studies MeSH Humans MeSH Lewy Body Disease: cerebrospinal fluid MeSH Lewy Body Disease: metabolism MeSH Longitudinal Studies MeSH Male MeSH Parkinson Disease: cerebrospinal fluid MeSH Parkinson Disease: metabolism MeSH Protein Aggregates: physiology MeSH alpha-Synuclein: biosynthesis MeSH alpha-Synuclein: cerebrospinal fluid MeSH Kunadt, Marcel P:(DE-HGF)0 1 Kruse, Niels P:(DE-HGF)0 2 Bartels, Claudia P:(DE-HGF)0 3 Moebius, Wiebke P:(DE-HGF)0 4 Danzer, Karin M P:(DE-2719)9001513 5 dzne Mollenhauer, Brit P:(DE-HGF)0 6 Schneider, Anja P:(DE-2719)2812035 7 Last author 10.1093/brain/awv346 : Oxford University Press (OUP), 2015-12-08 2 481-494 journal-article Crossref Brain 139 2015 0006-8950 10.1093/brain/awv346 Vol. 139, no. Pt 2, p. 481 - 494 PERI:(DE-600)1474117-9 2 139:Pt 2<481 - 494 481-494 Brain 139 2016 0006-8950 OpenAccess http://pub.dzne.de/record/138377/files/DZNE-2020-04699.pdf OpenAccess pdfa http://pub.dzne.de/record/138377/files/DZNE-2020-04699.pdf?subformat=pdfa Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4805087 oai:pub.dzne.de:138377 openaire open_access VDB driver dnbdelivery External Institute I:(DE-HGF)0 Extern 5 P:(DE-2719)9001513 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2812035 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 0 2016 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS Creative Commons Attribution-NonCommercial CC BY-NC 4.0 LIC:(DE-HGF)CCBYNC4 HGFVOC DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search JCR 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