Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology
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 th...
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doaj-de64c6dc9f24462181d9ca2696d705452020-11-25T01:52:42ZengBMCActa Neuropathologica Communications2051-59602017-06-015111010.1186/s40478-017-0445-5Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathologyJennifer Ngolab0Ivy Trinh1Edward Rockenstein2Michael Mante3Jazmin Florio4Margarita Trejo5Deborah Masliah6Anthony Adame7Eliezer Masliah8Robert A. Rissman9Department of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineDepartment of Neurosciences, UCSD School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s40478-017-0445-5Alzheimer’s diseaseExosomesAlpha synucleinLewy bodyTauAmyloid beta |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jennifer Ngolab Ivy Trinh Edward Rockenstein Michael Mante Jazmin Florio Margarita Trejo Deborah Masliah Anthony Adame Eliezer Masliah Robert A. Rissman |
spellingShingle |
Jennifer Ngolab Ivy Trinh Edward Rockenstein Michael Mante Jazmin Florio Margarita Trejo Deborah Masliah Anthony Adame Eliezer Masliah Robert A. Rissman Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology Acta Neuropathologica Communications Alzheimer’s disease Exosomes Alpha synuclein Lewy body Tau Amyloid beta |
author_facet |
Jennifer Ngolab Ivy Trinh Edward Rockenstein Michael Mante Jazmin Florio Margarita Trejo Deborah Masliah Anthony Adame Eliezer Masliah Robert A. Rissman |
author_sort |
Jennifer Ngolab |
title |
Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology |
title_short |
Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology |
title_full |
Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology |
title_fullStr |
Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology |
title_full_unstemmed |
Brain-derived exosomes from dementia with Lewy bodies propagate α-synuclein pathology |
title_sort |
brain-derived exosomes from dementia with lewy bodies propagate α-synuclein pathology |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2017-06-01 |
description |
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. |
topic |
Alzheimer’s disease Exosomes Alpha synuclein Lewy body Tau Amyloid beta |
url |
http://link.springer.com/article/10.1186/s40478-017-0445-5 |
work_keys_str_mv |
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