TY  - JOUR
AU  - Stuendl, Anne
AU  - Kunadt, Marcel
AU  - Kruse, Niels
AU  - Bartels, Claudia
AU  - Moebius, Wiebke
AU  - Danzer, Karin M
AU  - Mollenhauer, Brit
AU  - Schneider, Anja
TI  - Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson's disease and dementia with Lewy bodies.
JO  - Brain
VL  - 139
IS  - 2
SN  - 0006-8950
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DZNE-2020-04699
SP  - 481-494
PY  - 2016
AB  - 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.
KW  - Cerebrospinal Fluid: metabolism
KW  - Cohort Studies
KW  - Cross-Sectional Studies
KW  - Exosomes: metabolism
KW  - Female
KW  - Follow-Up Studies
KW  - Humans
KW  - Lewy Body Disease: cerebrospinal fluid
KW  - Lewy Body Disease: metabolism
KW  - Longitudinal Studies
KW  - Male
KW  - Parkinson Disease: cerebrospinal fluid
KW  - Parkinson Disease: metabolism
KW  - Protein Aggregates: physiology
KW  - alpha-Synuclein: biosynthesis
KW  - alpha-Synuclein: cerebrospinal fluid
KW  - Protein Aggregates (NLM Chemicals)
KW  - alpha-Synuclein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26647156
C2  - pmc:PMC4805087
DO  - DOI:10.1093/brain/awv346
UR  - https://pub.dzne.de/record/138377
ER  -