Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson’s disease and dementia with Lewy bodies
Anne Stuendl,Marcel Kunadt,Niels Kruse,Claudia Bartels,Wiebke Moebius,Karin M Danzer,Brit Mollenhauer,Anja Schneider +7 more
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TLDR
CSF exosomes of patients with Parkinson’s disease or dementia with Lewy bodies contain α- synuclein and induce α-synuclein aggregation in a reporter cell line, indicating that exosome support may support inter-neuronal transmission of α- Synuclein pathology.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.read more
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References
More filters
Journal ArticleDOI
Staging of brain pathology related to sporadic Parkinson’s disease
TL;DR: This study traces the course of the pathology in incidental and symptomatic Parkinson cases proposing a staging procedure based upon the readily recognizable topographical extent of the lesions.
Journal ArticleDOI
Diagnosis and management of dementia with Lewy bodies: Third report of the DLB Consortium
Ian G. McKeith,Ian G. McKeith,Dennis W. Dickson,James Lowe,Murat Emre,John T. O'Brien,Howard Feldman,Jeffrey L. Cummings,John E. Duda,Carol F. Lippa,Elaine K. Perry,Dag Aarsland,Hiroyuki Arai,Clive Ballard,B. F. Boeve,David J. Burn,Durval C. Costa,T. Del Ser,Bruno Dubois,Douglas Galasko,Serge Gauthier,Christopher G. Goetz,Estrella Gómez-Tortosa,Glenda M. Halliday,L. A. Hansen,John Hardy,Takeshi Iwatsubo,Raj N. Kalaria,Daniel I. Kaufer,Rose Anne Kenny,Amos D. Korczyn,Kenji Kosaka,Virginia M.-Y. Lee,Andrew J. Lees,Irene Litvan,Elisabet Londos,Oscar L. Lopez,Satoshi Minoshima,Yoshikuni Mizuno,José Antonio Molina,Elizabeta B. Mukaetova-Ladinska,Florence Pasquier,Robert H. Perry,Jörg B. Schulz,John Q. Trojanowski,Masahito Yamada +45 more
TL;DR: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them as mentioned in this paper.
Journal ArticleDOI
α-Synuclein in filamentous inclusions of Lewy bodies from Parkinson’s disease and dementia with Lewy bodies
TL;DR: It is shown thatLewy bodies and Lewy neurites from Parkinson’s disease and dementia with Lewy bodies are stained strongly by antibodies directed against amino- terminal and carboxyl-terminal sequences of α-synuclein, showing the presence of full- length or close to full-length α- synuclein.
Journal ArticleDOI
Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) Report of the NINDS-SPSP International Workshop*
Irene Litvan,Yves Agid,Donald B. Calne,G. Campbell,Bruno Dubois,Roger C. Duvoisin,Christopher G. Goetz,Lawrence I. Golbe,Jordan Grafman,John H. Growdon,Mark Hallett,Joseph Jankovic,Niall Quinn,Eva Tolosa,David S. Zee +14 more
TL;DR: Criteria that support the diagnosis of progressive supranuclear palsy, and that exclude diseases often confused with PSP, are presented.
Journal ArticleDOI
Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Nontransgenic Mice
Kelvin C. Luk,Victoria M. Kehm,Jenna C. Carroll,Bin Zhang,Patrick O’Brien,John Q. Trojanowski,Virginia M.-Y. Lee +6 more
TL;DR: It is found that in wild-type nontransgenic mice, a single intrastriatal inoculation of synthetic α- Syn fibrils led to the cell-to-cell transmission of pathologic α-Syn and Parkinson’s-like Lewy pathology in anatomically interconnected regions.