Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid

<div><p>α-Synuclein aggregates, a key hallmark of the pathogenesis of Parkinson’s disease, can be amplified by using their seeding activity, and the evaluation of the seeding activity of cerebrospinal fluid (CSF) is reportedly useful for diagnosis. However, conventional shaking-based ass...

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Main Author: Keita Kakuda (9668898) (author)
Other Authors: Kensuke Ikenaka (280400) (author), Katsuya Araki (2620255) (author), Masatomo So (1532092) (author), César Aguirre (18615127) (author), Yuta Kajiyama (11843735) (author), Kuni Konaka (18615130) (author), Kentaro Noi (5181488) (author), Kousuke Baba (818824) (author), Hiroshi Tsuda (209228) (author), Seiichi Nagano (9668904) (author), Takuma Ohmichi (718120) (author), Yoshitaka Nagai (115940) (author), Takahiko Tokuda (105837) (author), Omar M. A. El-Agnaf (8809331) (author), Hirotsugu Ogi (5181491) (author), Yuji Goto (573359) (author), Hideki Mochizuki (204792) (author)
Published: 2019
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_version_ 1864513513994584064
author Keita Kakuda (9668898)
author2 Kensuke Ikenaka (280400)
Katsuya Araki (2620255)
Masatomo So (1532092)
César Aguirre (18615127)
Yuta Kajiyama (11843735)
Kuni Konaka (18615130)
Kentaro Noi (5181488)
Kousuke Baba (818824)
Hiroshi Tsuda (209228)
Seiichi Nagano (9668904)
Takuma Ohmichi (718120)
Yoshitaka Nagai (115940)
Takahiko Tokuda (105837)
Omar M. A. El-Agnaf (8809331)
Hirotsugu Ogi (5181491)
Yuji Goto (573359)
Hideki Mochizuki (204792)
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author_facet Keita Kakuda (9668898)
Kensuke Ikenaka (280400)
Katsuya Araki (2620255)
Masatomo So (1532092)
César Aguirre (18615127)
Yuta Kajiyama (11843735)
Kuni Konaka (18615130)
Kentaro Noi (5181488)
Kousuke Baba (818824)
Hiroshi Tsuda (209228)
Seiichi Nagano (9668904)
Takuma Ohmichi (718120)
Yoshitaka Nagai (115940)
Takahiko Tokuda (105837)
Omar M. A. El-Agnaf (8809331)
Hirotsugu Ogi (5181491)
Yuji Goto (573359)
Hideki Mochizuki (204792)
author_role author
dc.creator.none.fl_str_mv Keita Kakuda (9668898)
Kensuke Ikenaka (280400)
Katsuya Araki (2620255)
Masatomo So (1532092)
César Aguirre (18615127)
Yuta Kajiyama (11843735)
Kuni Konaka (18615130)
Kentaro Noi (5181488)
Kousuke Baba (818824)
Hiroshi Tsuda (209228)
Seiichi Nagano (9668904)
Takuma Ohmichi (718120)
Yoshitaka Nagai (115940)
Takahiko Tokuda (105837)
Omar M. A. El-Agnaf (8809331)
Hirotsugu Ogi (5181491)
Yuji Goto (573359)
Hideki Mochizuki (204792)
dc.date.none.fl_str_mv 2019-04-12T03:00:00Z
dc.identifier.none.fl_str_mv 10.1038/s41598-019-42399-0
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Ultrasonication-based_rapid_amplification_of_-synuclein_aggregates_in_cerebrospinal_fluid/25904425
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biomedical and clinical sciences
Neurosciences
Seeding activity
Cerebrospinal fluid (CSF)
Diagnosis
High-throughput assay
Ultrasonication-induced amyloid fibrillation assay
Clinical indicators
Oligomers
dc.title.none.fl_str_mv Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>α-Synuclein aggregates, a key hallmark of the pathogenesis of Parkinson’s disease, can be amplified by using their seeding activity, and the evaluation of the seeding activity of cerebrospinal fluid (CSF) is reportedly useful for diagnosis. However, conventional shaking-based assays are time-consuming procedures, and the clinical significance of the diversity of seeding activity among patients remains to be clarified. Previously, we reported a high-throughput ultrasonication-induced amyloid fibrillation assay. Here, we adapted this assay to amplify and detect α-synuclein aggregates from CSF, and investigated the correlation between seeding activity and clinical indicators. We confirmed that this assay could detect α-synuclein aggregates prepared in vitro and also aggregates released from cultured cells. The seeding activity of CSF correlated with the levels of α-synuclein oligomers measured by an enzyme-linked immunosorbent assay. Moreover, the seeding activity of CSF from patients with Parkinson’s disease was higher than that of control patients. Notably, the lag time of patients with Parkinson’s disease was significantly correlated with the MIBG heart-to-mediastinum ratio. These findings showed that our ultrasonication-based assay can rapidly amplify misfolded α-synuclein and can evaluate the seeding activity of CSF.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-019-42399-0" target="_blank">https://dx.doi.org/10.1038/s41598-019-42399-0</a></p>
eu_rights_str_mv openAccess
id Manara2_546ad1ebefdc5627f5901a982c5a2917
identifier_str_mv 10.1038/s41598-019-42399-0
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25904425
publishDate 2019
repository.mail.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluidKeita Kakuda (9668898)Kensuke Ikenaka (280400)Katsuya Araki (2620255)Masatomo So (1532092)César Aguirre (18615127)Yuta Kajiyama (11843735)Kuni Konaka (18615130)Kentaro Noi (5181488)Kousuke Baba (818824)Hiroshi Tsuda (209228)Seiichi Nagano (9668904)Takuma Ohmichi (718120)Yoshitaka Nagai (115940)Takahiko Tokuda (105837)Omar M. A. El-Agnaf (8809331)Hirotsugu Ogi (5181491)Yuji Goto (573359)Hideki Mochizuki (204792)Biomedical and clinical sciencesNeurosciencesSeeding activityCerebrospinal fluid (CSF)DiagnosisHigh-throughput assayUltrasonication-induced amyloid fibrillation assayClinical indicatorsOligomers<div><p>α-Synuclein aggregates, a key hallmark of the pathogenesis of Parkinson’s disease, can be amplified by using their seeding activity, and the evaluation of the seeding activity of cerebrospinal fluid (CSF) is reportedly useful for diagnosis. However, conventional shaking-based assays are time-consuming procedures, and the clinical significance of the diversity of seeding activity among patients remains to be clarified. Previously, we reported a high-throughput ultrasonication-induced amyloid fibrillation assay. Here, we adapted this assay to amplify and detect α-synuclein aggregates from CSF, and investigated the correlation between seeding activity and clinical indicators. We confirmed that this assay could detect α-synuclein aggregates prepared in vitro and also aggregates released from cultured cells. The seeding activity of CSF correlated with the levels of α-synuclein oligomers measured by an enzyme-linked immunosorbent assay. Moreover, the seeding activity of CSF from patients with Parkinson’s disease was higher than that of control patients. Notably, the lag time of patients with Parkinson’s disease was significantly correlated with the MIBG heart-to-mediastinum ratio. These findings showed that our ultrasonication-based assay can rapidly amplify misfolded α-synuclein and can evaluate the seeding activity of CSF.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-019-42399-0" target="_blank">https://dx.doi.org/10.1038/s41598-019-42399-0</a></p>2019-04-12T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-019-42399-0https://figshare.com/articles/journal_contribution/Ultrasonication-based_rapid_amplification_of_-synuclein_aggregates_in_cerebrospinal_fluid/25904425CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259044252019-04-12T03:00:00Z
spellingShingle Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
Keita Kakuda (9668898)
Biomedical and clinical sciences
Neurosciences
Seeding activity
Cerebrospinal fluid (CSF)
Diagnosis
High-throughput assay
Ultrasonication-induced amyloid fibrillation assay
Clinical indicators
Oligomers
status_str publishedVersion
title Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
title_full Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
title_fullStr Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
title_full_unstemmed Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
title_short Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
title_sort Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
topic Biomedical and clinical sciences
Neurosciences
Seeding activity
Cerebrospinal fluid (CSF)
Diagnosis
High-throughput assay
Ultrasonication-induced amyloid fibrillation assay
Clinical indicators
Oligomers