{"keyword":["general chemical engineering","general chemistry"],"language":[{"iso":"eng"}],"acknowledgement":"We acknowledge support from Peterhouse (T.C.T.M.), the Swiss National Science foundation (T.C.T.M.), the Royal Society (A.Š.), the Academy of Medical Sciences (A.Š.), the UCL Institute for the Physics of Living Systems (S.C.), Sidney Sussex College (G.M.), the Wellcome Trust (A.Š., M.V., C.M.D. and T.P.J.K.), the Schiff Foundation (A.J.D.), the Cambridge Centre for Misfolding Diseases (M.V., C.M.D. and T.P.J.K.), the BBSRC (C.M.D. and T.P.J.K.), the Frances and Augustus Newman Foundation (T.P.J.K.), the Swedish Research Council (S.L.) and the ERC grant MAMBA (S.L., agreement no. 340890). The research that led to these results received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt (agreement no. 337969).","article_processing_charge":"No","intvolume":"        12","month":"04","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1038/s41557-020-0468-6"}]},"article_type":"original","publication_identifier":{"issn":["1755-4330"],"eissn":["1755-4349"]},"type":"journal_article","date_created":"2021-11-26T09:15:13Z","abstract":[{"text":"Oligomeric species populated during the aggregation of the Aβ42 peptide have been identified as potent cytotoxins linked to Alzheimer’s disease, but the fundamental molecular pathways that control their dynamics have yet to be elucidated. By developing a general approach that combines theory, experiment and simulation, we reveal, in molecular detail, the mechanisms of Aβ42 oligomer dynamics during amyloid fibril formation. Even though all mature amyloid fibrils must originate as oligomers, we found that most Aβ42 oligomers dissociate into their monomeric precursors without forming new fibrils. Only a minority of oligomers converts into fibrillar structures. Moreover, the heterogeneous ensemble of oligomeric species interconverts on timescales comparable to those of aggregation. Our results identify fundamentally new steps that could be targeted by therapeutic interventions designed to combat protein misfolding diseases.","lang":"eng"}],"main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2020.01.08.897488","open_access":"1"}],"citation":{"apa":"Michaels, T. C. T., Šarić, A., Curk, S., Bernfur, K., Arosio, P., Meisl, G., … Knowles, T. P. J. (2020). Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide. <i>Nature Chemistry</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41557-020-0452-1\">https://doi.org/10.1038/s41557-020-0452-1</a>","chicago":"Michaels, Thomas C. T., Anđela Šarić, Samo Curk, Katja Bernfur, Paolo Arosio, Georg Meisl, Alexander J. Dear, et al. “Dynamics of Oligomer Populations Formed during the Aggregation of Alzheimer’s Aβ42 Peptide.” <i>Nature Chemistry</i>. Springer Nature, 2020. <a href=\"https://doi.org/10.1038/s41557-020-0452-1\">https://doi.org/10.1038/s41557-020-0452-1</a>.","ieee":"T. C. T. Michaels <i>et al.</i>, “Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide,” <i>Nature Chemistry</i>, vol. 12, no. 5. Springer Nature, pp. 445–451, 2020.","mla":"Michaels, Thomas C. T., et al. “Dynamics of Oligomer Populations Formed during the Aggregation of Alzheimer’s Aβ42 Peptide.” <i>Nature Chemistry</i>, vol. 12, no. 5, Springer Nature, 2020, pp. 445–51, doi:<a href=\"https://doi.org/10.1038/s41557-020-0452-1\">10.1038/s41557-020-0452-1</a>.","ista":"Michaels TCT, Šarić A, Curk S, Bernfur K, Arosio P, Meisl G, Dear AJ, Cohen SIA, Dobson CM, Vendruscolo M, Linse S, Knowles TPJ. 2020. Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide. Nature Chemistry. 12(5), 445–451.","short":"T.C.T. Michaels, A. Šarić, S. Curk, K. Bernfur, P. Arosio, G. Meisl, A.J. Dear, S.I.A. Cohen, C.M. Dobson, M. Vendruscolo, S. Linse, T.P.J. Knowles, Nature Chemistry 12 (2020) 445–451.","ama":"Michaels TCT, Šarić A, Curk S, et al. Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide. <i>Nature Chemistry</i>. 2020;12(5):445-451. doi:<a href=\"https://doi.org/10.1038/s41557-020-0452-1\">10.1038/s41557-020-0452-1</a>"},"year":"2020","publication":"Nature Chemistry","pmid":1,"date_updated":"2021-11-26T11:21:08Z","issue":"5","oa":1,"title":"Dynamics of oligomer populations formed during the aggregation of Alzheimer’s Aβ42 peptide","publication_status":"published","external_id":{"pmid":["32303714"]},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","extern":"1","publisher":"Springer Nature","page":"445-451","volume":12,"quality_controlled":"1","_id":"10351","doi":"10.1038/s41557-020-0452-1","oa_version":"None","author":[{"first_name":"Thomas C. T.","full_name":"Michaels, Thomas C. T.","last_name":"Michaels"},{"last_name":"Šarić","full_name":"Šarić, Anđela","orcid":"0000-0002-7854-2139","first_name":"Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b"},{"full_name":"Curk, Samo","last_name":"Curk","first_name":"Samo"},{"first_name":"Katja","full_name":"Bernfur, Katja","last_name":"Bernfur"},{"first_name":"Paolo","full_name":"Arosio, Paolo","last_name":"Arosio"},{"last_name":"Meisl","full_name":"Meisl, Georg","first_name":"Georg"},{"first_name":"Alexander J.","last_name":"Dear","full_name":"Dear, Alexander J."},{"last_name":"Cohen","full_name":"Cohen, Samuel I. A.","first_name":"Samuel I. A."},{"last_name":"Dobson","full_name":"Dobson, Christopher M.","first_name":"Christopher M."},{"first_name":"Michele","last_name":"Vendruscolo","full_name":"Vendruscolo, Michele"},{"full_name":"Linse, Sara","last_name":"Linse","first_name":"Sara"},{"last_name":"Knowles","full_name":"Knowles, Tuomas P. J.","first_name":"Tuomas P. J."}],"status":"public","day":"13","date_published":"2020-04-13T00:00:00Z","scopus_import":"1"}