Journal Article

DZNE-2020-04699

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies.

Stuendl, A. ; Kunadt, M. ; Kruse, N. ; Bartels, C. ; Moebius, W. ; Danzer, K. M.Extern* ; Mollenhauer, B. ; Schneider, A. (Last author)DZNE*

2016
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/brain/awv346

Abstract: 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.

Keyword(s): 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) ; Protein Aggregates ; alpha-Synuclein

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Contributing Institute(s):

1. Translational Dementia Research Göttingen (AG Schneider Göttingen)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2016

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Database coverage:
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