{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:51:48Z","timestamp":1791949908133,"version":"4.3.4"},"reference-count":66,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MC_UP_A025-1013"],"award-info":[{"award-number":["MC_UP_A025-1013"]}]},{"award":["MC_UP_A025-1013"],"award-info":[{"award-number":["MC_UP_A025-1013"]}],"id":[{"id":"https:\/\/ror.org\/03x94j517","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Medical Research Council","award":["MC_U105184291"],"award-info":[{"award-number":["MC_U105184291"]}]},{"award":["MC_U105184291"],"award-info":[{"award-number":["MC_U105184291"]}],"id":[{"id":"https:\/\/ror.org\/03x94j517","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Churchill Fellowship"}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>The assembly of tau into amyloid filaments is associated with more than 20 neurodegenerative diseases, collectively termed tauopathies. Electron cryo-microscopy (cryo-EM) structures of brain-derived tau filaments revealed that specific structures define different diseases, triggering a quest for the development of experimental model systems that replicate the structures of disease. Here, we describe 12 phosphomimetic serine\/threonine-to-aspartate mutations in tau, which we term PAD12, that collectively induce the in vitro assembly of full-length three-repeat tau into filaments with the same structure as paired helical filaments extracted from the brains of individuals with Alzheimer\u2019s disease. Solution-state nuclear magnetic resonance spectroscopy suggests that phosphomimetic mutations in the carboxy-terminal domain of tau may facilitate filament formation by disrupting an intramolecular interaction between two IVYK motifs. PAD12 tau can be used for both nucleation-dependent and multiple rounds of seeded assembly in vitro, as well as for the seeding of tau biosensor cells. PAD12 tau can be assembled into paired helical filaments under various shaking conditions, with the resulting filaments being stable for extended periods of time. They can be labelled with fluorophores and biotin. Tau filaments extracted from the brains of individuals with Alzheimer\u2019s disease have been known to be made of hyperphosphorylated and abnormally phosphorylated full-length tau, but it was not known if the presence of this post-translational modification is more than a mere correlation. Our findings suggest that hyperphosphorylation of tau may be sufficient for the formation of the Alzheimer tau fold. PAD12 tau will be a useful tool for the study of molecular mechanisms of neurodegeneration.<\/jats:p>","DOI":"10.7554\/elife.104778","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T14:26:50Z","timestamp":1737037610000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.104778","source":"Crossref","is-referenced-by-count":10,"title":["Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments"],"prefix":"10.7554","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2152-1476","authenticated-orcid":true,"given":"Sofia","family":"L\u00f6vestam","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00tw3jy02","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Laboratory of Molecular Biology","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jane L","family":"Wagstaff","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00tw3jy02","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Laboratory of Molecular Biology","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Taxiarchis","family":"Katsinelos","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00tw3jy02","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Laboratory of Molecular Biology","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jenny","family":"Shi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00tw3jy02","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Laboratory of Molecular Biology","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Stefan MV","family":"Freund","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00tw3jy02","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Laboratory of Molecular Biology","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5214-7886","authenticated-orcid":true,"given":"Michel","family":"Goedert","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00tw3jy02","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Laboratory of Molecular Biology","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0462-6540","authenticated-orcid":true,"given":"Sjors HW","family":"Scheres","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00tw3jy02","id-type":"ROR","asserted-by":"publisher"}],"name":"MRC Laboratory of Molecular Biology","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119952119","type":"journal-article","article-title":"Cryo-EM structure of RNA-induced tau fibrils reveals a small C-terminal core that may nucleate fibril formation","volume":"119","author":"Abskharon","year":"2022","journal-title":"PNAS"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1002\/1873-3468.13675","type":"journal-article","article-title":"Tau (297-391) forms filaments that structurally mimic the core of paired helical filaments in Alzheimer\u2019s disease brain","volume":"594","author":"Al-Hilaly","year":"2020","journal-title":"FEBS Letters"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"30851","DOI":"10.1074\/jbc.M110.110957","type":"journal-article","article-title":"Phosphorylation of tau at Thr212, Thr231, and Ser262 combined causes neurodegeneration","volume":"285","author":"Alonso","year":"2010","journal-title":"The Journal of Biological Chemistry"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.ultramic.2013.06.004","type":"journal-article","article-title":"High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy","volume":"135","author":"Chen","year":"2013","journal-title":"Ultramicroscopy"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/BF00197809","type":"journal-article","article-title":"NMRPipe: a multidimensional spectral processing system based on UNIX pipes","volume":"6","author":"Delaglio","year":"1995","journal-title":"Journal of Biomolecular NMR"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1111\/jnc.15144","type":"journal-article","article-title":"Knockin\u2019 on heaven\u2019s door: Molecular mechanisms of neuronal tau uptake","volume":"156","author":"De Rocque","year":"2021","journal-title":"Journal of Neurochemistry"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"9080","DOI":"10.1073\/pnas.1708448114","type":"journal-article","article-title":"Identification of the Tau phosphorylation pattern that drives its aggregation","volume":"114","author":"Despres","year":"2017","journal-title":"PNAS"},{"key":"bib8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107730","type":"journal-article","article-title":"Alzheimer\u2019s disease seeded tau forms paired helical filaments yet lacks seeding potential","volume":"300","author":"Duan","year":"2024","journal-title":"The Journal of Biological Chemistry"},{"key":"bib9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107326","type":"journal-article","article-title":"Milligram-scale assembly and NMR fingerprint of tau fibrils adopting the Alzheimer\u2019s disease fold","volume":"300","author":"Duan","year":"2024","journal-title":"The Journal of Biological Chemistry"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"2991","DOI":"10.1038\/s41596-018-0075-9","type":"journal-article","article-title":"Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins","volume":"13","author":"Elegheert","year":"2018","journal-title":"Nature Protocols"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1038\/nature23002","type":"journal-article","article-title":"Cryo-EM structures of tau filaments from Alzheimer\u2019s disease","volume":"547","author":"Fitzpatrick","year":"2017","journal-title":"Nature"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1038\/srep27459","type":"journal-article","article-title":"IVA cloning: A single-tube universal cloning system exploiting bacterial In Vivo Assembly","volume":"6","author":"Garc\u00eda-Nafr\u00eda","year":"2016","journal-title":"Scientific Reports"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1021\/acs.biochem.3c00425","type":"journal-article","article-title":"Reconstitution of the Alzheimer\u2019s disease tau core structure from recombinant tau297-391 yields variable quaternary structures as seen by negative stain and cryo-EM","volume":"63","author":"Glynn","year":"2024","journal-title":"Biochemistry"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/0896-6273(89)90210-9","type":"journal-article","article-title":"Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer\u2019s disease","volume":"3","author":"Goedert","year":"1989","journal-title":"Neuron"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/0896-6273(92)90117-v","type":"journal-article","article-title":"Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms","volume":"8","author":"Goedert","year":"1992","journal-title":"Neuron"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/383550a0","type":"journal-article","article-title":"Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans","volume":"383","author":"Goedert","year":"1996","journal-title":"Nature"},{"key":"bib17","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0021-9258(18)48531-6","type":"journal-article","article-title":"Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau","volume":"267","author":"Greenberg","year":"1992","journal-title":"The Journal of Biological Chemistry"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"4913","DOI":"10.1073\/pnas.83.13.4913","type":"journal-article","article-title":"Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology","volume":"83","author":"Grundke-Iqbal","year":"1986","journal-title":"PNAS"},{"key":"bib19","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1046\/j.1471-4159.2003.02287.x","type":"journal-article","article-title":"Pseudophosphorylation of tau protein alters its ability for self-aggregation","volume":"88","author":"Haase","year":"2004","journal-title":"Journal of Neurochemistry"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1038\/nrneurol.2015.225","type":"journal-article","article-title":"Tau and neurodegenerative disease: the story so far","volume":"12","author":"Iqbal","year":"2016","journal-title":"Nature Reviews. Neurology"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"32066","DOI":"10.1074\/jbc.M805300200","type":"journal-article","article-title":"Proline-directed pseudo-phosphorylation at AT8 and PHF1 epitopes induces a compaction of the paperclip folding of Tau and generates a pathological (MC-1) conformation","volume":"283","author":"Jeganathan","year":"2008","journal-title":"The Journal of Biological Chemistry"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1023\/B:JNMR.0000042954.99056.ad","type":"journal-article","article-title":"Mars -- robust automatic backbone assignment of proteins","volume":"30","author":"Jung","year":"2004","journal-title":"Journal of Biomolecular NMR"},{"key":"bib23","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/s0014-5793(96)01386-5","type":"journal-article","article-title":"RNA stimulates aggregation of microtubule-associated protein tau into Alzheimer-like paired helical filaments","volume":"399","author":"Kampers","year":"1996","journal-title":"FEBS Letters"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.5281\/zenodo.4281064","type":"software","article-title":"Ekatrukha\/comdet: comdet 0.5.3","volume-title":"Zenodo","author":"Katrukha","year":"2020","unstructured":"Katrukha E. 2020. Ekatrukha\/comdet: comdet 0.5.3. Zenodo. https:\/\/doi.org\/10.5281\/zenodo.4281064."},{"key":"bib25","doi-asserted-by":"publisher","first-page":"5556","DOI":"10.1002\/anie.201100370","type":"journal-article","article-title":"Accelerated NMR spectroscopy by using compressed sensing","volume":"50","author":"Kazimierczuk","year":"2011","journal-title":"Angewandte Chemie"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/s10858-011-9472-x","type":"journal-article","article-title":"Random coil chemical shift for intrinsically disordered proteins: effects of temperature and pH","volume":"49","author":"Kjaergaard","year":"2011","journal-title":"Journal of Biomolecular NMR"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s10858-011-9508-2","type":"journal-article","article-title":"Sequence correction of random coil chemical shifts: correlation between neighbor correction factors and changes in the Ramachandran distribution","volume":"50","author":"Kjaergaard","year":"2011","journal-title":"Journal of Biomolecular NMR"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.tins.2022.01.006","type":"journal-article","article-title":"How do protein aggregates escape quality control in neurodegeneration?","volume":"45","author":"Koopman","year":"2022","journal-title":"Trends in Neurosciences"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1126\/science.1899488","type":"journal-article","article-title":"A68: a major subunit of paired helical filaments and derivatized forms of normal Tau","volume":"251","author":"Lee","year":"1991","journal-title":"Science"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1146\/annurev.neuro.24.1.1121","type":"journal-article","article-title":"Neurodegenerative tauopathies","volume":"24","author":"Lee","year":"2001","journal-title":"Annual Review of Neuroscience"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1093\/bioinformatics\/btab180","type":"journal-article","article-title":"POKY: a software suite for multidimensional NMR and 3D structure calculation of biomolecules","volume":"37","author":"Lee","year":"2021","journal-title":"Bioinformatics"},{"key":"bib32","doi-asserted-by":"crossref","first-page":"5301","DOI":"10.1016\/S0021-9258(17)42989-9","type":"journal-article","article-title":"Phosphorylation affects the ability of tau protein to promote microtubule assembly","volume":"259","author":"Lindwall","year":"1984","journal-title":"The Journal of Biological Chemistry"},{"key":"bib33","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.76494","type":"journal-article","article-title":"Assembly of recombinant tau into filaments identical to those of Alzheimer\u2019s disease and chronic traumatic encephalopathy","volume":"11","author":"L\u00f6vestam","year":"2022","journal-title":"eLife"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1039\/d2fd00034b","type":"journal-article","article-title":"High-throughput cryo-EM structure determination of amyloids","volume":"240","author":"L\u00f6vestam","year":"2022","journal-title":"Faraday Discussions"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41586-023-06788-w","type":"journal-article","article-title":"Disease-specific tau filaments assemble via polymorphic intermediates","volume":"625","author":"L\u00f6vestam","year":"2024","journal-title":"Nature"},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2316175121","type":"journal-article","article-title":"Structures of AT8 and PHF1 phosphomimetic tau: Insights into the posttranslational modification code of tau aggregation","volume":"121","author":"Mammeri","year":"2024","journal-title":"PNAS"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1073\/pnas.1607215114","type":"journal-article","article-title":"Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation","volume":"114","author":"McEwan","year":"2017","journal-title":"PNAS"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/BF00227819","type":"journal-article","article-title":"Monoclonal antibodies with selective specificity for Alzheimer Tau are directed against phosphatase-sensitive epitopes","volume":"84","author":"Mercken","year":"1992","journal-title":"Acta Neuropathologica"},{"key":"bib39","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1002\/j.1460-2075.1993.tb05665.x","type":"journal-article","article-title":"Molecular characterization of the minimal protease resistant tau unit of the Alzheimer\u2019s disease paired helical filament","volume":"12","author":"Novak","year":"1993","journal-title":"The EMBO Journal"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1046\/j.1471-4159.1996.67031183.x","type":"journal-article","article-title":"Polymerization of tau into filaments in the presence of heparin: the minimal sequence required for tau-tau interaction","volume":"67","author":"P\u00e9rez","year":"1996","journal-title":"Journal of Neurochemistry"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","type":"journal-article","article-title":"Prions","volume":"95","author":"Prusiner","year":"1998","journal-title":"PNAS"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.jsb.2015.08.008","type":"journal-article","article-title":"CTFFIND4: Fast and accurate defocus estimation from electron micrographs","volume":"192","author":"Rohou","year":"2015","journal-title":"Journal of Structural Biology"},{"key":"bib43","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/nmeth.2115","type":"journal-article","article-title":"Prevention of overfitting in cryo-EM structure determination","volume":"9","author":"Scheres","year":"2012","journal-title":"Nature Methods"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1107\/S2059798319016577","type":"journal-article","article-title":"Amyloid structure determination in RELION-3.1","volume":"76","author":"Scheres","year":"2020","journal-title":"Acta Crystallographica. Section D, Structural Biology"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41586-023-06437-2","type":"journal-article","article-title":"Molecular pathology of neurodegenerative diseases by cryo-EM of amyloids","volume":"621","author":"Scheres","year":"2023","journal-title":"Nature"},{"key":"bib46","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","type":"journal-article","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nature Methods"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"2970","DOI":"10.1021\/ja003760i","type":"journal-article","article-title":"Sequence-dependent correction of random coil NMR chemical shifts","volume":"123","author":"Schwarzinger","year":"2001","journal-title":"Journal of the American Chemical Society"},{"key":"bib48","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-023-01658-y","type":"journal-article","article-title":"Cryo-EM structures of tau filaments from the brains of mice transgenic for human mutant P301S Tau","volume":"11","author":"Schweighauser","year":"2023","journal-title":"Acta Neuropathologica Communications"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1038\/s41594-025-01575-9","type":"journal-article","article-title":"Distinct tau filament folds in human MAPT mutants P301L and P301T","volume":"32","author":"Schweighauser","year":"2025","journal-title":"Nature Structural & Molecular Biology"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41586-021-03911-7","type":"journal-article","article-title":"Structure-based classification of tauopathies","volume":"598","author":"Shi","year":"2021","journal-title":"Nature"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1002\/2211-5463.13657","type":"journal-article","article-title":"Cryo-EM structures of tau filaments from SH-SY5Y cells seeded with brain extracts from cases of Alzheimer\u2019s disease and corticobasal degeneration","volume":"13","author":"Tarutani","year":"2023","journal-title":"FEBS Open Bio"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1016\/j.cell.2020.10.029","type":"journal-article","article-title":"Tau PTM profiles identify patient heterogeneity and stages of alzheimer\u2019s disease","volume":"183","author":"Wesseling","year":"2020","journal-title":"Cell"},{"key":"bib53","first-page":"2181","type":"journal-article","article-title":"Free fatty acids stimulate the polymerization of tau and amyloid beta peptides: In vitro evidence for a common effector of pathogenesis in Alzheimer\u2019s disease","volume":"150","author":"Wilson","year":"1997","journal-title":"The American Journal of Pathology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"4884","DOI":"10.1073\/pnas.85.13.4884","type":"journal-article","article-title":"Structural characterization of the core of the paired helical filament of Alzheimer disease","volume":"85","author":"Wischik","year":"1988","journal-title":"PNAS"},{"key":"bib55","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.43584","type":"journal-article","article-title":"Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer\u2019s and Pick\u2019s diseases","volume":"8","author":"Zhang","year":"2019","journal-title":"eLife"},{"key":"bib56","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-023-00637-w","type":"journal-article","article-title":"Cryo-EM structures reveal variant Tau amyloid fibrils between the rTg4510 mouse model and sporadic human tauopathies","volume":"10","author":"Zhao","year":"2024","journal-title":"Cell Discovery"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1107\/S205225251801463X","type":"journal-article","article-title":"A Bayesian approach to beam-induced motion correction in cryo-EM single-particle analysis","volume":"6","author":"Zivanov","year":"2019","journal-title":"IUCrJ"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1107\/S2052252520000081","type":"journal-article","article-title":"Estimation of high-order aberrations and anisotropic magnification from cryo-EM data sets in RELION-3.1","volume":"7","author":"Zivanov","year":"2020","journal-title":"IUCrJ"},{"key":"dataset1","doi-asserted-by":"publisher","DOI":"10.2210\/pdb9h5g\/pdb","type":"dataset","article-title":"PAD12 0N3R:0N4R tau PHF","volume-title":"Worldwide Protein Data Bank","author":"Lovestam","year":"2024","unstructured":"Lovestam S, Scheres SHW, Goedert M. 2024. PAD12 0N3R:0N4R tau PHF. Worldwide Protein Data Bank."},{"key":"dataset2","doi-asserted-by":"publisher","DOI":"10.2210\/pdb9h5j\/pdb","type":"dataset","article-title":"PAD12 0N3R tau PHF seeded by AD","volume-title":"Worldwide Protein Data Bank","author":"Lovestam","year":"2024","unstructured":"Lovestam S, Scheres SHW, Goedert M. 2024. PAD12 0N3R tau PHF seeded by AD. Worldwide Protein Data Bank."},{"key":"dataset3","doi-asserted-by":"publisher","DOI":"10.2210\/pdb9s2b\/pdb","type":"dataset","article-title":"297-441 delta392-395 tau filaments","volume-title":"Worldwide Protein Data Bank","author":"Lovestam","year":"2024","unstructured":"Lovestam S, Scheres SHW, Goedert M. 2024. 297-441 delta392-395 tau filaments. Worldwide Protein Data Bank."},{"key":"dataset4","doi-asserted-by":"publisher","DOI":"10.13018\/BMR52694","type":"dataset","article-title":"Tau297-441 wt","volume-title":"Biological Magnetic Resonance Data Bank","author":"Lovestam","year":"2026","unstructured":"Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau297-441 wt. Biological Magnetic Resonance Data Bank."},{"key":"dataset5","doi-asserted-by":"publisher","DOI":"10.13018\/BMR52695","type":"dataset","article-title":"Tau297-441 PAD12","volume-title":"Biological Magnetic Resonance Data Bank","author":"Lovestam","year":"2026","unstructured":"Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau297-441 PAD12. Biological Magnetic Resonance Data Bank."},{"key":"dataset6","doi-asserted-by":"publisher","DOI":"10.13018\/BMR52696","type":"dataset","article-title":"Tau 151-391 WT","volume-title":"Biological Magnetic Resonance Data Bank","author":"Lovestam","year":"2026","unstructured":"Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau 151-391 WT. Biological Magnetic Resonance Data Bank."},{"key":"dataset7","doi-asserted-by":"publisher","DOI":"10.13018\/BMR52697","type":"dataset","article-title":"Tau151-391 PAD12","volume-title":"Biological Magnetic Resonance Data Bank","author":"Lovestam","year":"2026","unstructured":"Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau151-391 PAD12. Biological Magnetic Resonance Data Bank."},{"key":"dataset8","doi-asserted-by":"publisher","DOI":"10.13018\/BMR53230","type":"dataset","article-title":"Tau297-441 delta","volume-title":"Biological Magnetic Resonance Data Bank","author":"Lovestam","year":"2026","unstructured":"Lovestam S, Wagstaff J, Freund S, Scheres S. 2026. Tau297-441 delta. Biological Magnetic Resonance Data Bank."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/104778\/elife-104778-v1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/104778\/elife-104778-v1.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/104778","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T08:57:48Z","timestamp":1787561868000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/104778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":66,"alternative-id":["10.7554\/eLife.104778"],"URL":"https:\/\/doi.org\/10.7554\/elife.104778","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.10.23.619846","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2024.10.23.619846","asserted-by":"object"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.104778.4","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.104778.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.104778.2","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.104778.3","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"doi","id":"10.2210\/pdb9h5g\/pdb","asserted-by":"subject"},{"id-type":"doi","id":"10.2210\/pdb9h5j\/pdb","asserted-by":"subject"},{"id-type":"doi","id":"10.2210\/pdb9s2b\/pdb","asserted-by":"subject"},{"id-type":"doi","id":"10.13018\/BMR52694","asserted-by":"subject"},{"id-type":"doi","id":"10.13018\/BMR52695","asserted-by":"subject"},{"id-type":"doi","id":"10.13018\/BMR52696","asserted-by":"subject"},{"id-type":"doi","id":"10.13018\/BMR52697","asserted-by":"subject"},{"id-type":"doi","id":"10.13018\/BMR53230","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP104778"}}