Brain-derived Exosomes from Dementia with Lewy Bodies Propagate α-synuclein Pathology

Overview

Journal Acta Neuropathol Commun

Publisher Biomed Central

Specialty Neurology

Date 2017 Jun 11

PMID 28599681

Citations 120

Authors

Jennifer Ngolab

Ivy Trinh

Edward Rockenstein

Michael Mante

Jazmin Florio

Margarita Trejo

Deborah Masliah

Anthony Adame

Eliezer Masliah

Robert A Rissman

Affiliations

Soon will be listed here.

Abstract

Proteins implicated in neurodegenerative conditions such as Alzheimer's disease (AD) and Dementia with Lewy Bodies (DLB) have been identified in bodily fluids encased in extracellular vesicles called exosomes. Whether exosomes found in DLB patients can transmit pathology is not clear. In this study, exosomes were successfully harvested through ultracentrifugation from brain tissue from DLB and AD patients as well as non-diseased brain tissue. Exosomes extracted from brains diagnosed with either AD or DLB contained aggregate-prone proteins. Furthermore, injection of brain-derived exosomes from DLB patients into the brains of wild type mice induced α-synuclein (α-syn) aggregation. As assessed through immunofluorescent double labeling, α-syn aggregation was observed in MAP2, Rab5 neurons. Using a neuronal cell line, we also identified intracellular α-syn aggregation mediated by exosomes is dependent on recipient cell endocytosis. Together, these data suggest that exosomes from DLB patients are sufficient for seeding and propagating α-syn aggregation in vivo.

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