%0 Journal Article
%A Stuendl, Anne
%A Kunadt, Marcel
%A Kruse, Niels
%A Bartels, Claudia
%A Moebius, Wiebke
%A Danzer, Karin M
%A Mollenhauer, Brit
%A Schneider, Anja
%T Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies.
%J Brain
%V 139
%N 2
%@ 0006-8950
%C Oxford
%I Oxford Univ. Press
%M DZNE-2020-04699
%P 481-494
%D 2016
%X 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.
%K Cerebrospinal Fluid: metabolism
%K Cohort Studies
%K Cross-Sectional Studies
%K Exosomes: metabolism
%K Female
%K Follow-Up Studies
%K Humans
%K Lewy Body Disease: cerebrospinal fluid
%K Lewy Body Disease: metabolism
%K Longitudinal Studies
%K Male
%K Parkinson Disease: cerebrospinal fluid
%K Parkinson Disease: metabolism
%K Protein Aggregates: physiology
%K alpha-Synuclein: biosynthesis
%K alpha-Synuclein: cerebrospinal fluid
%K Protein Aggregates (NLM Chemicals)
%K alpha-Synuclein (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:26647156
%2 pmc:PMC4805087
%R 10.1093/brain/awv346
%U https://pub.dzne.de/record/138377