{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T03:48:13Z","timestamp":1793245693508,"version":"4.5.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T00:00:00Z","timestamp":1706918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T00:00:00Z","timestamp":1706918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tauopathies encompass a group of neurodegenerative disorders characterised by diverse tau amyloid fibril structures. The persistence of polymorphism across tauopathies suggests that distinct pathological conditions dictate the adopted polymorph for each disease. However, the extent to which intrinsic structural tendencies of tau amyloid cores contribute to fibril polymorphism remains uncertain. Using a combination of experimental approaches, we here identify a new amyloidogenic motif, PAM4 (Polymorphic Amyloid Motif of Repeat 4), as a significant contributor to tau polymorphism. Calculation of per-residue contributions to the stability of the fibril cores of different pathologic tau structures suggests that PAM4 plays a central role in preserving structural integrity across amyloid polymorphs. Consistent with this, cryo-EM structural analysis of fibrils formed from a synthetic PAM4 peptide shows that the sequence adopts alternative structures that closely correspond to distinct disease-associated tau strains. Furthermore, in-cell experiments revealed that PAM4 deletion hampers the cellular seeding efficiency of tau aggregates extracted from Alzheimer\u2019s disease, corticobasal degeneration, and progressive supranuclear palsy patients, underscoring PAM4\u2019s pivotal role in these tauopathies. Together, our results highlight the importance of the intrinsic structural propensity of amyloid core segments to determine the structure of tau in cells, and in propagating amyloid structures in disease.<\/jats:p>","DOI":"10.1038\/s41467-024-45429-2","type":"journal-article","created":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T07:01:54Z","timestamp":1706943714000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Local structural preferences in shaping tau amyloid polymorphism"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4030-1022","authenticated-orcid":false,"given":"Nikolaos","family":"Louros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5490-613X","authenticated-orcid":false,"given":"Martin","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grigoria","family":"Tsaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meine","family":"Ramakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5632-888X","authenticated-orcid":false,"given":"Chiara","family":"Morelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Gallardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"D\u2019Haeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Goossens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Audenaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1036-1075","authenticated-orcid":false,"given":"Dietmar Rudolf","family":"Thal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R.","family":"Mackenzie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4049-0863","authenticated-orcid":false,"given":"Rosa","family":"Rademakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3640-5275","authenticated-orcid":false,"given":"Neil A.","family":"Ranson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-8039","authenticated-orcid":false,"given":"Sheena E.","family":"Radford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9189-7399","authenticated-orcid":false,"given":"Frederic","family":"Rousseau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2020-0168","authenticated-orcid":false,"given":"Joost","family":"Schymkowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,3]]},"reference":[{"key":"45429_CR1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/B978-0-12-802395-2.00025-0","volume":"145","author":"GG Kovacs","year":"2017","unstructured":"Kovacs, G. G. Tauopathies. Handb. Clin. Neurol. 145, 355\u2013368 (2017).","journal-title":"Handb. Clin. Neurol."},{"key":"45429_CR2","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/0896-6273(89)90210-9","volume":"3","author":"M Goedert","year":"1989","unstructured":"Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D. & Crowther, R. A. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer\u2019s disease. Neuron 3, 519\u2013526 (1989).","journal-title":"Neuron"},{"key":"45429_CR3","doi-asserted-by":"publisher","first-page":"10526","DOI":"10.1021\/bi800783d","volume":"47","author":"S Jeganathan","year":"2008","unstructured":"Jeganathan, S., von Bergen, M., Mandelkow, E. M. & Mandelkow, E. The natively unfolded character of tau and its aggregation to Alzheimer-like paired helical filaments. Biochemistry 47, 10526\u201310539 (2008).","journal-title":"Biochemistry"},{"key":"45429_CR4","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.2174\/092986708785909111","volume":"15","author":"CX Gong","year":"2008","unstructured":"Gong, C. X. & Iqbal, K. Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Curr. Med Chem. 15, 2321\u20132328 (2008).","journal-title":"Curr. Med Chem."},{"key":"45429_CR5","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1016\/j.cell.2020.10.029","volume":"183","author":"H Wesseling","year":"2020","unstructured":"Wesseling, H. et al. Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer\u2019s Disease. Cell 183, 1699\u20131713 e1613 (2020).","journal-title":"Cell"},{"key":"45429_CR6","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1038\/ncb1901","volume":"11","author":"F Clavaguera","year":"2009","unstructured":"Clavaguera, F. et al. Transmission and spreading of tauopathy in transgenic mouse brain. Nat. Cell Biol. 11, 909\u2013913 (2009).","journal-title":"Nat. Cell Biol."},{"key":"45429_CR7","doi-asserted-by":"publisher","first-page":"12845","DOI":"10.1074\/jbc.M808759200","volume":"284","author":"B Frost","year":"2009","unstructured":"Frost, B., Jacks, R. L. & Diamond, M. I. Propagation of tau misfolding from the outside to the inside of a cell. J. Biol. Chem. 284, 12845\u201312852 (2009).","journal-title":"J. Biol. Chem."},{"key":"45429_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28955-9","volume":"13","author":"N Louros","year":"2022","unstructured":"Louros, N. et al. Mapping the sequence specificity of heterotypic amyloid interactions enables the identification of aggregation modifiers. Nat. Commun. 13, 1351 (2022).","journal-title":"Nat. Commun."},{"key":"45429_CR9","doi-asserted-by":"publisher","first-page":"e2119952119","DOI":"10.1073\/pnas.2119952119","volume":"119","author":"R Abskharon","year":"2022","unstructured":"Abskharon, R. et al. Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation. Proc. Natl Acad. Sci. USA 119, e2119952119 (2022).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"45429_CR10","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.sbi.2021.11.007","volume":"72","author":"N Louros","year":"2022","unstructured":"Louros, N., Schymkowitz, J. & Rousseau, F. Heterotypic amyloid interactions: Clues to polymorphic bias and selective cellular vulnerability? Curr. Opin. Struct. Biol. 72, 176\u2013186 (2022).","journal-title":"Curr. Opin. Struct. Biol."},{"key":"45429_CR11","doi-asserted-by":"publisher","first-page":"11406","DOI":"10.1523\/JNEUROSCI.1230-17.2017","volume":"37","author":"S Narasimhan","year":"2017","unstructured":"Narasimhan, S. et al. Pathological Tau Strains from Human Brains Recapitulate the Diversity of Tauopathies in Nontransgenic Mouse Brain. J. Neurosci. 37, 11406\u201311423 (2017).","journal-title":"J. Neurosci."},{"key":"45429_CR12","doi-asserted-by":"publisher","unstructured":"Louros, N., Schymkowitz, J. & Rousseau, F. Mechanisms and pathology of protein misfolding and aggregation. Nat. Rev. Mol. Cell Biol. https:\/\/doi.org\/10.1038\/s41580-023-00647-2 (2023).","DOI":"10.1038\/s41580-023-00647-2"},{"key":"45429_CR13","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.sbi.2020.05.011","volume":"64","author":"SH Scheres","year":"2020","unstructured":"Scheres, S. H., Zhang, W., Falcon, B. & Goedert, M. Cryo-EM structures of tau filaments. Curr. Opin. Struct. Biol. 64, 17\u201325 (2020).","journal-title":"Curr. Opin. Struct. Biol."},{"key":"45429_CR14","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41586-021-03911-7","volume":"598","author":"Y Shi","year":"2021","unstructured":"Shi, Y. et al. Structure-based classification of tauopathies. Nature 598, 359\u2013363 (2021).","journal-title":"Nature"},{"key":"45429_CR15","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1016\/j.cell.2020.01.027","volume":"180","author":"T Arakhamia","year":"2020","unstructured":"Arakhamia, T. et al. Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains. Cell 180, 633\u2013644 e612 (2020).","journal-title":"Cell"},{"key":"45429_CR16","doi-asserted-by":"publisher","first-page":"E313","DOI":"10.1073\/pnas.1212100110","volume":"110","author":"S Wegmann","year":"2013","unstructured":"Wegmann, S., Medalsy, I. D., Mandelkow, E. & Muller, D. J. The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush. Proc. Natl Acad. Sci. USA 110, E313\u2013E321 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"45429_CR17","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/S0165-0173(00)00019-9","volume":"33","author":"L Buee","year":"2000","unstructured":"Buee, L., Bussiere, T., Buee-Scherrer, V., Delacourte, A. & Hof, P. R. Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res. Brain Res Rev. 33, 95\u2013130 (2000).","journal-title":"Brain Res Rev."},{"key":"45429_CR18","doi-asserted-by":"publisher","first-page":"48165","DOI":"10.1074\/jbc.M105196200","volume":"276","author":"M von Bergen","year":"2001","unstructured":"von Bergen, M. et al. Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local beta-structure. J. Biol. Chem. 276, 48165\u201348174 (2001).","journal-title":"J. Biol. Chem."},{"key":"45429_CR19","doi-asserted-by":"publisher","first-page":"5129","DOI":"10.1073\/pnas.97.10.5129","volume":"97","author":"M von Bergen","year":"2000","unstructured":"von Bergen, M. et al. Assembly of \u03c4 protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming \u03b2 structure. Proc. Natl Acad. Sci. 97, 5129\u20135134 (2000).","journal-title":"Proc. Natl Acad. Sci."},{"key":"45429_CR20","doi-asserted-by":"publisher","unstructured":"van der Kant, R., Louros, N., Schymkowitz, J. & Rousseau, F. Thermodynamic analysis of amyloid fibril structures reveals a common framework for stability in amyloid polymorphs. Structure, https:\/\/doi.org\/10.1016\/j.str.2022.05.002 (2022).","DOI":"10.1016\/j.str.2022.05.002"},{"key":"45429_CR21","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41586-018-0454-y","volume":"561","author":"B Falcon","year":"2018","unstructured":"Falcon, B. et al. Structures of filaments from Pick\u2019s disease reveal a novel tau protein fold. Nature 561, 137\u2013140 (2018).","journal-title":"Nature"},{"key":"45429_CR22","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nature23002","volume":"547","author":"AWP Fitzpatrick","year":"2017","unstructured":"Fitzpatrick, A. W. P. et al. Cryo-EM structures of tau filaments from Alzheimer\u2019s disease. Nature 547, 185\u2013190 (2017).","journal-title":"Nature"},{"key":"45429_CR23","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00401-021-02301-7","volume":"142","author":"J Vaquer-Alicea","year":"2021","unstructured":"Vaquer-Alicea, J., Diamond, M. I. & Joachimiak, L. A. Tau strains shape disease. Acta Neuropathol. 142, 57\u201371 (2021).","journal-title":"Acta Neuropathol."},{"key":"45429_CR24","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1038\/nmeth.1432","volume":"7","author":"S Maurer-Stroh","year":"2010","unstructured":"Maurer-Stroh, S. et al. Exploring the sequence determinants of amyloid structure using position-specific scoring matrices. Nat. Methods 7, 237\u2013242 (2010).","journal-title":"Nat. Methods"},{"key":"45429_CR25","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17207-3","volume":"11","author":"N Louros","year":"2020","unstructured":"Louros, N., Orlando, G., De Vleeschouwer, M., Rousseau, F. & Schymkowitz, J. Structure-based machine-guided mapping of amyloid sequence space reveals uncharted sequence clusters with higher solubilities. Nat. Commun. 11, 3314 (2020).","journal-title":"Nat. Commun."},{"key":"45429_CR26","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jcis.2020.03.075","volume":"573","author":"E Arad","year":"2020","unstructured":"Arad, E., Green, H., Jelinek, R. & Rapaport, H. Revisiting thioflavin T (ThT) fluorescence as a marker of protein fibrillation \u2013 The prominent role of electrostatic interactions. J. Colloid Interface Sci. 573, 87\u201395 (2020).","journal-title":"J. Colloid Interface Sci."},{"key":"45429_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36572-3","volume":"14","author":"V Mullapudi","year":"2023","unstructured":"Mullapudi, V. et al. Network of hotspot interactions cluster tau amyloid folds. Nat. Commun. 14, 895 (2023).","journal-title":"Nat. Commun."},{"key":"45429_CR28","doi-asserted-by":"publisher","unstructured":"Lovestam, S. et al. Assembly of recombinant tau into filaments identical to those of Alzheimer\u2019s disease and chronic traumatic encephalopathy. Elife 11, https:\/\/doi.org\/10.7554\/eLife.76494 (2022).","DOI":"10.7554\/eLife.76494"},{"key":"45429_CR29","doi-asserted-by":"publisher","unstructured":"Zhang, W. et al. Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer\u2019s and Pick\u2019s diseases. Elife 8, https:\/\/doi.org\/10.7554\/eLife.43584 (2019).","DOI":"10.7554\/eLife.43584"},{"key":"45429_CR30","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.tibs.2021.12.009","volume":"47","author":"BD Ryder","year":"2022","unstructured":"Ryder, B. D., Wydorski, P. M., Hou, Z. & Joachimiak, L. A. Chaperoning shape-shifting tau in disease. Trends Biochemical Sci. 47, 301\u2013313 (2022).","journal-title":"Trends Biochemical Sci."},{"key":"45429_CR31","doi-asserted-by":"publisher","unstructured":"Kumar, S. T. et al. Seeding the aggregation of TDP-43 requires post-fibrillization proteolytic cleavage. Nat. Neurosci. https:\/\/doi.org\/10.1038\/s41593-023-01341-4 (2023).","DOI":"10.1038\/s41593-023-01341-4"},{"key":"45429_CR32","doi-asserted-by":"publisher","first-page":"e202200499","DOI":"10.1002\/cbic.202200499","volume":"23","author":"R Sharma","year":"2022","unstructured":"Sharma, R., Tomar, S., Puri, S. & Wangoo, N. Self-Assembled Peptide Hydrogel for Accelerated Wound Healing: Impact of N-Terminal and C-Terminal Modifications. ChemBioChem 23, e202200499 (2022).","journal-title":"ChemBioChem"},{"key":"45429_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10355-1","volume":"10","author":"D Chen","year":"2019","unstructured":"Chen, D. et al. Tau local structure shields an amyloid-forming motif and controls aggregation propensity. Nat. Commun. 10, 2493 (2019).","journal-title":"Nat. Commun."},{"key":"45429_CR34","doi-asserted-by":"publisher","first-page":"6207","DOI":"10.1016\/j.cell.2021.11.029","volume":"184","author":"T Arakhamia","year":"2021","unstructured":"Arakhamia, T. et al. Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains. Cell 184, 6207\u20136210 (2021).","journal-title":"Cell"},{"key":"45429_CR35","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s00401-018-1914-z","volume":"136","author":"B Falcon","year":"2018","unstructured":"Falcon, B. et al. Tau filaments from multiple cases of sporadic and inherited Alzheimer\u2019s disease adopt a common fold. Acta Neuropathol. 136, 699\u2013708 (2018).","journal-title":"Acta Neuropathol."},{"key":"45429_CR36","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1038\/s41586-020-2043-0","volume":"580","author":"W Zhang","year":"2020","unstructured":"Zhang, W. et al. Novel tau filament fold in corticobasal degeneration. Nature 580, 283\u2013287 (2020).","journal-title":"Nature"},{"key":"45429_CR37","doi-asserted-by":"publisher","first-page":"624302","DOI":"10.3389\/fmolb.2021.624302","volume":"8","author":"C Leonard","year":"2021","unstructured":"Leonard, C., Phillips, C. & McCarty, J. Insight Into Seeded Tau Fibril Growth From Molecular Dynamics Simulation of the Alzheimer\u2019s Disease Protofibril Core. Front. Mol. Biosci. 8, 624302 (2021).","journal-title":"Front. Mol. Biosci."},{"key":"45429_CR38","doi-asserted-by":"publisher","unstructured":"Seidler, P. M. et al. CryoEM reveals how the small molecule EGCG binds to Alzheimer\u2019s brain-derived tau fibrils and initiates fibril disaggregation. bioRxiv, https:\/\/doi.org\/10.1101\/2020.05.29.124537 (2020).","DOI":"10.1101\/2020.05.29.124537"},{"key":"45429_CR39","doi-asserted-by":"publisher","first-page":"5700","DOI":"10.1039\/C8CC01263F","volume":"54","author":"X Li","year":"2018","unstructured":"Li, X. et al. The distinct structural preferences of tau protein repeat domains. Chem. Commun. (Camb.) 54, 5700\u20135703 (2018).","journal-title":"Chem. Commun. (Camb.)"},{"key":"45429_CR40","doi-asserted-by":"publisher","first-page":"4059","DOI":"10.1002\/anie.201913001","volume":"59","author":"M Haj-Yahya","year":"2020","unstructured":"Haj-Yahya, M. et al. Site-Specific Hyperphosphorylation Inhibits, Rather than Promotes, Tau Fibrillization, Seeding Capacity, and Its Microtubule Binding. Angew. Chem. Int. Ed. 59, 4059\u20134067 (2020).","journal-title":"Angew. Chem. Int. Ed."},{"key":"45429_CR41","doi-asserted-by":"publisher","first-page":"2231","DOI":"10.1007\/s00018-020-03643-3","volume":"78","author":"Y Losev","year":"2021","unstructured":"Losev, Y. et al. Differential effects of putative N-glycosylation sites in human Tau on Alzheimer\u2019s disease-related neurodegeneration. Cell. Mol. Life Sci. 78, 2231\u20132245 (2021).","journal-title":"Cell. Mol. Life Sci."},{"key":"45429_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38537-y","volume":"14","author":"GE Merz","year":"2023","unstructured":"Merz, G. E. et al. Stacked binding of a PET ligand to Alzheimer\u2019s tau paired helical filaments. Nat. Commun. 14, 3048 (2023).","journal-title":"Nat. Commun."},{"key":"45429_CR43","doi-asserted-by":"publisher","unstructured":"Peter, K. et al. Cryo-EM structure of Alzheimer\u2019s disease tau filaments with PET ligand MK-6240. bioRxiv, https:\/\/doi.org\/10.1101\/2023.09.22.558671 (2023).","DOI":"10.1101\/2023.09.22.558671"},{"key":"45429_CR44","doi-asserted-by":"publisher","first-page":"D389","DOI":"10.1093\/nar\/gkz758","volume":"48","author":"N Louros","year":"2020","unstructured":"Louros, N. et al. WALTZ-DB 2.0: an updated database containing structural information of experimentally determined amyloid-forming peptides. Nucleic Acids Res. 48, D389\u2013D393 (2020).","journal-title":"Nucleic Acids Res."},{"key":"45429_CR45","doi-asserted-by":"publisher","unstructured":"Louros, N., van der Kant, R., Schymkowitz, J. & Rousseau, F. StAmP-DB: A platform for structures of polymorphic amyloid fibril cores. Bioinformatics, https:\/\/doi.org\/10.1093\/bioinformatics\/btac126 (2022).","DOI":"10.1093\/bioinformatics\/btac126"},{"key":"45429_CR46","doi-asserted-by":"publisher","first-page":"W590","DOI":"10.1093\/nar\/gkh477","volume":"32","author":"R Maiti","year":"2004","unstructured":"Maiti, R., Van Domselaar, G. H., Zhang, H. & Wishart, D. S. SuperPose: a simple server for sophisticated structural superposition. Nucleic Acids Res. 32, W590\u2013W594 (2004).","journal-title":"Nucleic Acids Res."},{"key":"45429_CR47","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1021\/ac60214a047","volume":"36","author":"A Savitzky","year":"1964","unstructured":"Savitzky, A. & Golay, M. J. E. Smoothing and Differentiation of Data by Simplified Least Squares Procedures. Anal. Chem. 36, 1627\u20131639 (1964).","journal-title":"Anal. Chem."},{"key":"45429_CR48","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/nmeth.4193","volume":"14","author":"SQ Zheng","year":"2017","unstructured":"Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331\u2013332 (2017).","journal-title":"Nat. Methods"},{"key":"45429_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jsb.2015.11.003","volume":"193","author":"K Zhang","year":"2016","unstructured":"Zhang, K. Gctf: Real-time CTF determination and correction. J. Struct. Biol. 193, 1\u201312 (2016).","journal-title":"J. Struct. Biol."},{"key":"45429_CR50","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1107\/S2059798320007342","volume":"76","author":"T Wagner","year":"2020","unstructured":"Wagner, T. et al. Two particle-picking procedures for filamentous proteins: SPHIRE-crYOLO filament mode and SPHIRE-STRIPER. Acta Crystallogr D. Struct. Biol. 76, 613\u2013620 (2020).","journal-title":"Acta Crystallogr D. Struct. Biol."},{"key":"45429_CR51","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1107\/S2059798319016577","volume":"76","author":"SHW Scheres","year":"2020","unstructured":"Scheres, S. H. W. Amyloid structure determination in RELION-3.1. Acta Crystallogr D. Struct. Biol. 76, 94\u2013\u2212101 (2020).","journal-title":"Acta Crystallogr D. Struct. Biol."},{"key":"45429_CR52","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr D. Biol. Crystallogr 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr D. Biol. Crystallogr"},{"key":"45429_CR53","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr D. Biol. Crystallogr 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr D. Biol. Crystallogr"},{"key":"45429_CR54","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1002\/pro.3330","volume":"27","author":"CJ Williams","year":"2018","unstructured":"Williams, C. J. et al. MolProbity: More and better reference data for improved all-atom structure validation. Protein Sci. 27, 293\u2013315 (2018).","journal-title":"Protein Sci."},{"key":"45429_CR55","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1006\/jsbi.1996.0013","volume":"116","author":"JR Kremer","year":"1996","unstructured":"Kremer, J. R., Mastronarde, D. N. & McIntosh, J. R. Computer visualization of three-dimensional image data using IMOD. J. Struct. Biol. 116, 71\u201376 (1996).","journal-title":"J. Struct. Biol."},{"key":"45429_CR56","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38495-5","volume":"14","author":"C Leistner","year":"2023","unstructured":"Leistner, C. et al. The in-tissue molecular architecture of \u03b2-amyloid pathology in the mammalian brain. Nat. Commun. 14, 2833 (2023).","journal-title":"Nat. Commun."},{"key":"45429_CR57","doi-asserted-by":"publisher","unstructured":"Mirbaha, H. et al. Inert and seed-competent tau monomers suggest structural origins of aggregation. Elife 7, https:\/\/doi.org\/10.7554\/eLife.36584 (2018).","DOI":"10.7554\/eLife.36584"},{"key":"45429_CR58","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/0896-6273(92)90117-V","volume":"8","author":"M Goedert","year":"1992","unstructured":"Goedert, M., Spillantini, M. G., Cairns, N. J. & Crowther, R. A. Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8, 159\u2013168 (1992).","journal-title":"Neuron"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-45429-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-45429-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-45429-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T12:36:53Z","timestamp":1707223013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-45429-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,3]]},"references-count":58,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["45429"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-45429-2","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,3]]},"assertion":[{"value":"23 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 January 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1028"}}