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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2019
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| _version_ | 1864513513994584064 |
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| 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 | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| 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 |