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

Kakuda, Keita; Ikenaka, Kensuke; Araki, Katsuya; So, Masatomo; Aguirre, César; Kajiyama, Yuta; Konaka, Kuni; Noi, Kentaro; Baba, Kousuke; Tsuda, Hiroshi; Nagano, Seiichi; Ohmichi, Takuma; Nagai, Yoshitaka; Tokuda, Takahiko; El-Agnaf, Omar M.A.; Ogi, Hirotsugu; Goto, Yuji; Mochizuki, Hideki

doi:https://doi.org/10.1038/s41598-019-42399-0

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

Kakuda, Keita; Ikenaka, Kensuke; Araki, Katsuya et al.

Scientific Reports, 2019, 9, 6001

Number of Access:2,260（2025-08-15 06:46 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93353

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Title	Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
Creator	NRID 1000020815500 1000020815500 researchmap permalink keitakakuda keitakakuda Scopus Author ID 57192154985 57192154985 CreatorName Kakuda, Keita
	NRID 1000070774058 1000070774058 researchmap permalink kensukeikenaka kensukeikenaka Scopus Author ID 8588484300 8588484300 CreatorName Ikenaka, Kensuke
	NRID 1000050649431 1000050649431 CreatorName Araki, Katsuya
	NRID 1000040746335 1000040746335 CreatorName So, Masatomo
	NRID 1000020865597 1000020865597 CreatorName Aguirre, César
	NRID 1000080792390 1000080792390 CreatorName Kajiyama, Yuta
	NRID 1000020393225 1000020393225 CreatorName Konaka, Kuni
	NRID 1000030588405 1000030588405 CreatorName Noi, Kentaro
	NRID 1000090750159 1000090750159 researchmap permalink 5017 5017 Scopus Author ID 7402227089 7402227089 CreatorName Baba, Kousuke
	NRID 1000000792095 1000000792095 CreatorName Tsuda, Hiroshi
	NRID 1000040362727 1000040362727 researchmap permalink read0106301 read0106301 Scopus Author ID 7103321284 7103321284 CreatorName Nagano, Seiichi
	NRID 1000060869288 1000060869288 CreatorName Ohmichi, Takuma
	NRID 1000060335354 1000060335354 CreatorName Nagai, Yoshitaka
	NRID 1000080242692 1000080242692 CreatorName Tokuda, Takahiko
	CreatorName El-Agnaf, Omar M.A.
	NRID 1000090252626 1000090252626 researchmap permalink read0042771 read0042771 Scopus Author ID 35563683500 35563683500 CreatorName Ogi, Hirotsugu
	NRID 1000040153770 1000040153770 CreatorName Goto, Yuji
	NRID 1000090230044 1000090230044 ORCID 0000-0002-0874-7542 0000-0002-0874-7542 researchmap permalink read0207787 read0207787 Scopus Author ID 7202006099 7202006099 CreatorName Mochizuki, Hideki
Description	Kakuda K., Ikenaka K., Araki K., et al. Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid. Scientific Reports 9, 6001 (2019); https://doi.org/10.1038/s41598-019-42399-0.
Abstract	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.
Publisher	Nature Publishing Group
Source Title	Scientific Reports
Volume (Issue)	9
Page	6001
Date of Issued	2019-04-12
Language	English
Handle URL	https://hdl.handle.net/11094/93353
eISSN	20452322
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1038/s41598-019-42399-0
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Scientific Reports. 2019, 9, p. 6001
DC.title	Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
DC.creator	Kakuda, Keita
	Ikenaka, Kensuke
	Araki, Katsuya
	So, Masatomo
	Aguirre, César
	Kajiyama, Yuta
	Konaka, Kuni
	Noi, Kentaro
	Baba, Kousuke
	Tsuda, Hiroshi
	Nagano, Seiichi
	Ohmichi, Takuma
	Nagai, Yoshitaka
	Tokuda, Takahiko
	El-Agnaf, Omar M.A.
	Ogi, Hirotsugu
	Goto, Yuji
	Mochizuki, Hideki
DC.publisher	Nature Publishing Group
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2019-04-12
DC.identifier	https://doi.org/10.1038/s41598-019-42399-0
DC.description	Kakuda K., Ikenaka K., Araki K., et al. Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid. Scientific Reports 9, 6001 (2019); https://doi.org/10.1038/s41598-019-42399-0.
DCTERMS.abstract	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.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	93353
citation_title	Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
citation_author	Kakuda, Keita
	Ikenaka, Kensuke
	Araki, Katsuya
	So, Masatomo
	Aguirre, César
	Kajiyama, Yuta
	Konaka, Kuni
	Noi, Kentaro
	Baba, Kousuke
	Tsuda, Hiroshi
	Nagano, Seiichi
	Ohmichi, Takuma
	Nagai, Yoshitaka
	Tokuda, Takahiko
	El-Agnaf, Omar M.A.
	Ogi, Hirotsugu
	Goto, Yuji
	Mochizuki, Hideki
citation_publisher	Nature Publishing Group
citation_language	English
citation_date	2019-04-12
citation_journal_title	Scientific Reports
citation_volume	9
citation_firstpage	6001
citation_doi	https://doi.org/10.1038/s41598-019-42399-0
citation_public_url	https://hdl.handle.net/11094/93353

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

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