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

アクセス数:2,250件（2025-07-31 04:34 集計）

固定URL: https://hdl.handle.net/11094/93353

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タイトル	Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid
著者	NRID 1000020815500 1000020815500 researchmap permalink keitakakuda keitakakuda Scopus Author ID 57192154985 57192154985 著者名 Kakuda, Keita
	NRID 1000070774058 1000070774058 researchmap permalink kensukeikenaka kensukeikenaka Scopus Author ID 8588484300 8588484300 著者名 Ikenaka, Kensuke
	NRID 1000050649431 1000050649431 著者名 Araki, Katsuya
	NRID 1000040746335 1000040746335 著者名 So, Masatomo
	NRID 1000020865597 1000020865597 著者名 Aguirre, César
	NRID 1000080792390 1000080792390 著者名 Kajiyama, Yuta
	NRID 1000020393225 1000020393225 著者名 Konaka, Kuni
	NRID 1000030588405 1000030588405 著者名 Noi, Kentaro
	NRID 1000090750159 1000090750159 researchmap permalink 5017 5017 Scopus Author ID 7402227089 7402227089 著者名 Baba, Kousuke
	NRID 1000000792095 1000000792095 著者名 Tsuda, Hiroshi
	NRID 1000040362727 1000040362727 researchmap permalink read0106301 read0106301 Scopus Author ID 7103321284 7103321284 著者名 Nagano, Seiichi
	NRID 1000060869288 1000060869288 著者名 Ohmichi, Takuma
	NRID 1000060335354 1000060335354 著者名 Nagai, Yoshitaka
	NRID 1000080242692 1000080242692 著者名 Tokuda, Takahiko
	著者名 El-Agnaf, Omar M.A.
	NRID 1000090252626 1000090252626 researchmap permalink read0042771 read0042771 Scopus Author ID 35563683500 35563683500 著者名 Ogi, Hirotsugu
	NRID 1000040153770 1000040153770 著者名 Goto, Yuji
	NRID 1000090230044 1000090230044 ORCID 0000-0002-0874-7542 0000-0002-0874-7542 researchmap permalink read0207787 read0207787 Scopus Author ID 7202006099 7202006099 著者名 Mochizuki, Hideki
内容	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.
抄録	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.
出版者	Nature Publishing Group
収録物名	Scientific Reports
巻(号)	9
ページ	6001
刊行年月	2019-04-12
言語	英語
ハンドルURL	https://hdl.handle.net/11094/93353
eISSN	20452322
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1038/s41598-019-42399-0
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	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	英語
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	英語
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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