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01.03.2016 | Original Paper

Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes

verfasst von: Corinna Bliederhaeuser, Veselin Grozdanov, Anna Speidel, Lisa Zondler, Wolfgang P. Ruf, Hanna Bayer, Martin Kiechle, Marisa S. Feiler, Axel Freischmidt, David Brenner, Anke Witting, Bastian Hengerer, Marcus Fändrich, Albert C. Ludolph, Jochen H. Weishaupt, Frank Gillardon, Karin M. Danzer

Erschienen in: Acta Neuropathologica | Ausgabe 3/2016

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Abstract

Extracellular alpha-synuclein (αsyn) oligomers, associated to exosomes or free, play an important role in the pathogenesis of Parkinson’s disease (PD). Increasing evidence suggests that these extracellular moieties activate microglia leading to enhanced neuronal damage. Despite extensive efforts on studying neuroinflammation in PD, little is known about the impact of age on microglial activation and phagocytosis, especially of extracellular αsyn oligomers. Here, we show that microglia isolated from adult mice, in contrast to microglia from young mice, display phagocytosis deficits of free and exosome-associated αsyn oligomers combined with enhanced TNFα secretion. In addition, we describe a dysregulation of monocyte subpopulations with age in mice and humans. Accordingly, human monocytes from elderly donors also show reduced phagocytic activity of extracellular αsyn. These findings suggest that these age-related alterations may contribute to an increased susceptibility to pathogens or abnormally folded proteins with age in neurodegenerative diseases.

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Titel: Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes
verfasst von: Corinna Bliederhaeuser
Veselin Grozdanov
Anna Speidel
Lisa Zondler
Wolfgang P. Ruf
Hanna Bayer
Martin Kiechle
Marisa S. Feiler
Axel Freischmidt
David Brenner
Anke Witting
Bastian Hengerer
Marcus Fändrich
Albert C. Ludolph
Jochen H. Weishaupt
Frank Gillardon
Karin M. Danzer
Publikationsdatum: 01.03.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Acta Neuropathologica / Ausgabe 3/2016
Print ISSN: 0001-6322
Elektronische ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-015-1504-2

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