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Cryo-EM structures of tau filaments from Alzheimer’s disease
Open accessAbstract
Alzheimer's disease is the most common neurodegenerative disease, and there are no mechanism-based therapies. The disease is defined by the presence of abundant neurofibrillary lesions and neuritic plaques in the cerebral cortex. Neurofibrillary lesions comprise paired helical and straight tau filaments, whereas tau filaments with different morphologies characterize other neurodegenerative diseases. No high-resolution structures of tau filaments are available. Here we present cryo-electron microscopy (cryo-EM) maps at 3.4-3.5 Å resolution and corresponding atomic models of paired helical and straight filaments from the brain of an individual with Alzheimer's disease. Filament cores are made of two identical protofilaments comprising residues 306-378 of tau protein, which adopt a combined cross-β/β-helix structure and define the seed for tau aggregation. Paired helical and straight filaments differ in their inter-protofilament packing, showing that they are ultrastructural polymorphs. These findings demonstrate that cryo-EM allows atomic characterization of amyloid filaments from patient-derived material, and pave the way for investigation of a range of neurodegenerative diseases.
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“ultra-structural analyses of tau filaments in brains from individuals with AD have shown that tau tangles contain both 3-repeat (3R)-tau and 4-repeat (4R)-tau isoforms (18)”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [18]
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“In AD, tau tangles contain a mixture of 3R- and 4R-tau isoforms to adopt an AD-characteristic topology (18, 19).”
From Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming (2024) · cites this paper as [18]
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“In AD, tau filaments assume a cross-β/β-helical fold (10).”
From MAP2 caps tau fibrils and inhibits aggregation (2023) · cites this paper as [10]
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“Misfolding and aberrant accumulation of Tau is a pathological hallmark of Alzheimer’s disease (AD)18, 19.”
From Multivalent cross-linking of actin filaments and microtubules through the microtubule-associated protein Tau (2017) · cites this paper as [19]
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Citations
Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
Refinement of Macromolecular Structures by the Maximum-Likelihood Method
Murshudov, G. N., Vagin, A. A., & Dodson, E. J. (1997) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444996012255 · Cited by 14,796
Self-citationMolProbity : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115
MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S. Q., Palovcak, E. J., Armache, J., Verba, K. A., Cheng, Y., & Agard, D. A. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,496
Protein Misfolding, Functional Amyloid, and Human Disease
Chiti, F., & Dobson, C. M. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.75.101304.123901 · Cited by 6,497
Gctf: Real-time CTF determination and correction
Zhang, K. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.11.003 · Cited by 3,417
Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D., & Crowther, R. A. (1989) · Neuron · doi:10.1016/0896-6273(89)90210-9 · Cited by 2,492
Self-citationAtomic structures of amyloid cross-β spines reveal varied steric zippers
Sawaya, M. R., Sambashivan, S., Nelson, R. A., Ivanova, M. I., Sievers, S. A., Apostol, M. I., Thompson, M. J., Balbirnie, M., Wiltzius, J. J. W., McFarlane, H. T., et al. (2007) · Nature · doi:10.1038/nature05695 · Cited by 2,279
Common core structure of amyloid fibrils by synchrotron X-ray diffraction 1 1Edited by F. E. Cohen
Sunde, M., Serpell, L. C., Bartlam, M. G., Fraser, P. E., Pepys, M. B., & Blake, C. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1348 · Cited by 1,735
Goedert, M., Spillantini, M. G., Cairns, N. J., & Crowther, R. A. (1992) · Neuron · doi:10.1016/0896-6273(92)90117-v · Cited by 1,122
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Lewis, A. J., Genoud, C., Pont, M., van de Berg, W. D. J., Frank, S., Stahlberg, H., Shahmoradian, S. H., & Al‐Amoudi, A. (2019) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2019.06.003 · Cited by 35
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Röder, C., Vettore, N., Mangels, L. N., Gremer, L., Ravelli, R. B. G., Willbold, D., Hoyer, W., Buell, A. K., & Schroeder, G. F. (2019) · Nature Communications · doi:10.1038/s41467-019-11320-8 · Cited by 36
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Shoeibi, A., Olfati, N., & Litvan, I. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.01125 · Cited by 39
Thermodynamics of amyloid fibril formation from chemical depolymerization
Vettore, N., & Buell, A. K. (2019) · Physical Chemistry Chemical Physics · doi:10.1039/c9cp04524d · Cited by 37
Meisl, G., Knowles, T. P. J., & Klenerman, D. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.01.010 · Cited by 37
Prifti, E., Tsakiri, E. N., Vourkou, E., Stamatakis, G. M., Samiotaki, M. K., & Papanikolopoulou, K. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1920-20.2020 · Cited by 39
Conformational fingerprinting of tau variants and strains by Raman spectroscopy
Devitt, G., Crisford, A., Rice, W., Weismiller, H. A., Fan, Z., Commins, C., Hyman, B. T., Margittai, M., Mahajan, S., & Mudher, A. K. (2021) · RSC Advances · doi:10.1039/d1ra00870f · Cited by 34
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Ruiz-Gabarre, D., Carnero-Espejo, A., Ávila, J., & García‐Escudero, V. (2022) · Cells · doi:10.3390/cells11050840 · Cited by 39
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Xie, T., Li, Y., Tian, C., Yuan, C., Dai, B., Wang, S., Zhou, K., Liu, J., Tan, H., Liang, Y., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00859 · Cited by 37
The molecular basis of Alzheimer's plaques
Pospich, S., & Raunser, S. (2017) · Science · doi:10.1126/science.aap8002 · Cited by 37
Network of hotspot interactions cluster tau amyloid folds
Mullapudi, V., Vaquer‐Alicea, J., Bommareddy, V., Vega, A. R., Ryder, B. D., White, C. L., Diamond, M. I., & Joachimiak, Ł. A. (2023) · Nature Communications · doi:10.1038/s41467-023-36572-3 · Cited by 36
“2b, c) [15, 17, 18, 20, 21].”
BackgroundMethodInfluentialTau truncation in the pathogenesis of Alzheimer’s disease: a narrative review
Chu, D., Yang, X., Wang, J., Zhou, Y., Gu, J., Miao, J., Wu, F., & Liu, F. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385853 · Cited by 39
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Arakawa, T., Niikura, T., Kita, Y. A., & Akuta, T. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46010040 · Cited by 36
“…clear that SLG was better than the other three detergents in preserving the transparency of the cornea and removing residual cellular nuclei and other components from the porcine cornea. transparency of the cornea and removing residual cellular nuclei and other components from the porcine cornea.”
BackgroundCryo-EM structures of pathogenic fibrils and their impact on neurodegenerative disease research
Todd, T. W., Islam, N. N., Cook, C. N., Caulfield, T. R., & Petrucelli, L. (2024) · Neuron · doi:10.1016/j.neuron.2024.05.012 · Cited by 37
Manger, L. H., Foote, A. K., Wood, S. L., Holden, M. R., Heylman, K. D., Margittai, M., & Goldsmith, R. H. (2017) · Angewandte Chemie International Edition · doi:10.1002/anie.201708242 · Cited by 36
Advances in protein misfolding, amyloidosis and its correlation with human diseases
Kundu, D., Prerna, K., Chaurasia, R., Bharty, M. K., & Dubey, V. K. (2020) · 3 Biotech · doi:10.1007/s13205-020-2166-x · Cited by 40
Burke, C. M., Walsh, D. J., Mark, K. M. K., Deleault, N. R., Nishina, K. A., Agrimi, U., Bari, M. A. D., & Supattapone, S. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008495 · Cited by 36
“Interestingly, AD filaments have a different molecular structure than CTE filaments[65, 66] and accumulate in different regions of the brain than CTE filaments[67].”
BackgroundApplication of yeast to studying amyloid and prion diseases
Chernoff, Y. O., Grizel, A. V., Rubel, A. A., Zelinsky, A. А., Chandramowlishwaran, P., & Chernova, T. A. (2020) · Advances in genetics · doi:10.1016/bs.adgen.2020.01.002 · Cited by 41
“Amyloid-forming core of tau filaments is located within the microtubule-binding repeat region (Fitzpatrick et al., 2017), which is polymorphic due to alternative splicing: isoforms containing from two to four repeats are detected (Andreadis, Brown, & Kosik, 1992; Goedert & Jakes, 1990).”
Proteopathic Seed Amplification Assays for Neurodegenerative Disorders
Ferreira, N., & Caughey, B. W. (2020) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2020.04.002 · Cited by 35
Jablonski, A. M., Warren, L., Usenovic, M., Zhou, H. H., Sugam, J. A., Parmentier‐Batteur, S., & Voleti, B. (2021) · Scientific Reports · doi:10.1038/s41598-021-82901-1 · Cited by 38
Montalbano, M., Majmundar, L., Sengupta, U., Fung, L., & Kayed, R. (2022) · Brain Pathology · doi:10.1111/bpa.13112 · Cited by 35
Receptor Recycling by Retromer
Carosi, J. M., Denton, D., Kumar, S., & Sargeant, T. J. (2023) · Molecular and Cellular Biology · doi:10.1080/10985549.2023.2222053 · Cited by 36
RT-QuIC detection of tauopathies using full-length tau substrates
Tennant, J. M., Henderson, D. M., Wisniewski, T. M., & Hoover, E. A. (2020) · Prion · doi:10.1080/19336896.2020.1832946 · Cited by 31
“Alzheimer’s disease and chronic traumatic encephalopathy (CTE) contain a mixture of 3 R and 4 R tau isoforms in the PHFs (3 R/4 R tauopathies) [8,9].”
BackgroundTDP-43 Proteinopathy and Tauopathy: Do They Have Pathomechanistic Links?
Riku, Y., Yoshida, M., Iwasaki, Y., Sobue, G., Katsuno, M., & Ishigaki, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415755 · Cited by 36
“Cryo-electron microscopy has revealed that tau-filament cores in AD patients are made of two identical protofilaments comprising residues V306–F378 of tau protein [49], whereas those in PiD patients consist of residues K254–F378 of 3R-tau [50]; these studies suggest that the molecular structures of misfolded tau diffe…”
BackgroundCascio, F. L., Park, S., Sengupta, U., Puangmalai, N., Bhatt, N. N., Shchankin, N., Jerez, C., Moreno, N., Bittar, A., Xavier, R., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-07499-w · Cited by 38
Dupré, E., Danis, C., Arrial, A., Hanoulle, X., Homa, M., Cantrelle, F., Merzougui, H., Colin, M., Rain, J., Buée, L., et al. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00217 · Cited by 37
Shiells, H., Schelter, B. O., Bentham, P., Baddeley, T. C., Rubino, C. M., Ganesan, H., Hammel, J., Vuksanović, V., Staff, R. T., Murray, A. D., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191173 · Cited by 34
Chen, Y. X., Ing, N. L., Wang, F., Xu, D., Sloan, N. B., Lam, N. T., Winter, D. L., Egelman, E. H., Hochbaum, A. I., Clark, D. S., et al. (2020) · ACS Nano · doi:10.1021/acsnano.9b09405 · Cited by 35
Genome-wide association study and functional validation implicates JADE1 in tauopathy
Farrell, K. W., Kim, S., Han, N., Iida, M. A., Gonzalez, E. M., Otero‐García, M., Walker, J. M., Richardson, T. E., Renton, A. E., Andrews, S. J., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02379-z · Cited by 36
Acosta, D. M., Mancinelli, C. D., Bracken, C., & Eliezer, D. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101442 · Cited by 36
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BackgroundSimrén, J., Brum, W. S., Ashton, N. J., Benedet, A. L., Karikari, T. K., Kvartsberg, H., Sjons, E., Lussier, F. Z., Chamoun, M., Stevenson, J., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01142-0 · Cited by 34
“In a similar manner, normalizing CSF tau368 to t-tau may lead to a better marker of tau aggregates, by correcting for shifting proteolytic processing and secretion of tau, with Nto mid-terminal tau truncated fragments being released into the CSF, and that more C-terminal species containing the aggregation-prone microt…”
BackgroundTau proteinopathies and the prion concept
(2020) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2020.08.003 · Cited by 38
Self-citationGiannini, L., Ohm, D. T., Rozemüller, A. J. M., Dratch, L., Suh, E. R., Deerlin, V. M. V., Trojanowski, J. Q., Lee, E. B., Swieten, J. C. V., Grossman, M., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02487-4 · Cited by 34
Hu, J., Sha, W., Yuan, S., Wu, J., & Huang, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241915023 · Cited by 40
“Unexpectedly, the structures of tau filaments are diverse in different types of tauopathy diseases [49].”
BackgroundOverlaps and divergences between tauopathies and synucleinopathies: a duet of neurodegeneration
Li, W., & Li, J. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00407-y · Cited by 37
Galpern, W. R., Triana‐Baltzer, G., Li, L., Kolen, K. V., Timmers, M., Haeverans, K., Janssens, L., Kolb, H. C., Nandy, P., Aida, K., et al. (2024) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2024.163 · Cited by 38
Microfluidic approaches for probing amyloid assembly and behaviour
Herling, T. W., Levin, A., Saar, K. L., Dobson, C. M., & Knowles, T. P. J. (2018) · Lab on a Chip · doi:10.1039/c7lc01241a · Cited by 34
Intrinsically disordered proteins in the formation of functional amyloids from bacteria to humans
Avni, A., Swasthi, H. M., Majumdar, A., & Mukhopadhyay, S. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.05.005 · Cited by 35
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Caruso, A., Nicoletti, F., Gaetano, A., & Scaccianoce, S. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00976 · Cited by 37
Viswanathan, G. K., Paul, A., Gazit, E., & Segal, D. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00242 · Cited by 34
“In line with this, the recently reported cryo-EM structure of Tau filaments suggests that the β-core of the filament comprises of eight β-sheets (β-1 to β-8) spanning the sequence between V306 and F378, amongst which β-1 is the PHF6 hexapeptide (Fitzpatrick et al., 2017).”
BackgroundXanthohumol inhibits tau protein aggregation and protects cells against tau aggregates
Zhang, M., Wu, Q., Yao, X., Zhao, J., Zhong, W., Liu, Q., & Xiao, S. (2019) · Food & Function · doi:10.1039/c9fo02133g · Cited by 33
Semisynthetic Modification of Tau Protein with Di-Ubiquitin Chains for Aggregation Studies
Munari, F., Barracchia, C. G., Parolini, F., Tira, R., Bubacco, L., Assfalg, M., & D’Onofrio, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21124400 · Cited by 34
“The solved structure of tau filaments purified from AD-brain revealed residues 306-378 as the ordered fibril core, with the N- and C termini forming the fuzzy coat [25].”
BackgroundAsher, D. M., Belay, E. D., Bigio, E. H., Brandner, S., Brubaker, S. A., Caughey, B. W., Clark, B., Damon, I. K., Diamond, M. I., Freund, M. P., et al. (2020) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlaa109 · Cited by 35
Secondary Nucleation and the Conservation of Structural Characteristics of Amyloid Fibril Strains
Alijanvand, S. H., Peduzzo, A., & Buell, A. K. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.669994 · Cited by 35
“, 2020), tau (Fitzpatrick et al., 2017) and immunoglobulin light chains (Radamaker et al.”
BackgroundTau Seeding Mouse Models with Patient Brain-Derived Aggregates
Robert, A., Schöll, M., & Vogels, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116132 · Cited by 37
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Lopez‐Silva, T. L., & Schneider, J. P. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2021.06.006 · Cited by 34
Structurally Distinct Polymorphs of Tau Aggregates Revealed by Nanoscale Infrared Spectroscopy
Banerjee, S., & Ghosh, A. (2021) · The Journal of Physical Chemistry Letters · doi:10.1021/acs.jpclett.1c02660 · Cited by 33
Hubbard, E. E., Heil, L. R., Merrihew, G. E., Chhatwal, J. P., Farlow, M. R., McLean, C., Ghetti, B. F., Newell, K. L., Frosch, M. P., Bateman, R. J., et al. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00558 · Cited by 33
Self-citationTau Protein and Frontotemporal Dementias
Goedert, M., Spillantini, M. G., Falcon, B., Zhang, W., Newell, K. L., Hasegawa, M., Scheres, S. H. W., & Ghetti, B. F. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51140-1_12 · Cited by 37
Self-citation“Prion-like” seeding and propagation of oligomeric protein assemblies in neurodegenerative disorders
Zampar, S., Gregorio, S. E. D., Grimmer, G., Watts, J. C., & Ingelsson, M. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1436262 · Cited by 39
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Jiji, A. C., Vahid, A. A., Reselammal, D. S., Shabana, P. S., Mehjubin, C. K., & Vijayan, V. (2017) · Chemistry - A European Journal · doi:10.1002/chem.201704555 · Cited by 33
Amyloidogenic cross-seeding of Tau protein: Transient emergence of structural variants of fibrils
Niżyński, B., Nieznańska, H., Dec, R., Boyko, S., Dzwolak, W., & Nieznański, K. (2018) · PLoS ONE · doi:10.1371/journal.pone.0201182 · Cited by 33
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Baggett, D. W., & Nath, A. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00581 · Cited by 34
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Tarutani, A., & Hasegawa, M. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.07.005 · Cited by 33
Conformational Evolution of Molecular Signatures during Amyloidogenic Protein Aggregation
Devitt, G., Rice, W., Crisford, A., Nandhakumar, I. S., Mudher, A. K., & Mahajan, S. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00451 · Cited by 33
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Hou, Z., Chen, D., Ryder, B. D., & Joachimiak, Ł. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-93093-z · Cited by 31
Xia, Y., Bell, B. M., & Giasson, B. I. (2021) · Scientific Reports · doi:10.1038/s41598-021-96627-7 · Cited by 34
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Giovannini, J., Smeralda, W., Jouanne, M., Santos, J. S. O., Catto, M., & Voisin‐Chiret, A. S. (2022) · Drug Discovery Today · doi:10.1016/j.drudis.2022.01.009 · Cited by 33
Meng, F., Yoo, J., & Chung, H. S. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2116736119 · Cited by 38
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Liu, Z., Zhu, Y. J., Zhang, L., Jiang, W., Liu, Y., Tang, Q., Cai, X., Li, J., Wang, L., Tao, C.-L., et al. (2022) · Science China Chemistry · doi:10.1007/s11426-022-1408-5 · Cited by 33
Structure of the nonhelical filament of the Alzheimer’s disease tau core
Duan, P., Dregni, A. J., Mammeri, N. E., & Hong, M. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2310067120 · Cited by 33
Townsend, D. J., Fullwood, N. J., Yates, E. A., & Middleton, D. A. (2020) · Biochemistry · doi:10.1021/acs.biochem.0c00443 · Cited by 32
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Bu, F., Dee, D. R., & Liu, B. (2024) · mBio · doi:10.1128/mbio.00419-24 · Cited by 32
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Coughlin, D. G., Dickson, D. W., Josephs, K. A., & Litvan, I. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51140-1_11 · Cited by 33
Solid-state NMR spectroscopic trends for supramolecular assemblies and protein aggregates
Linser, R. (2017) · Solid State Nuclear Magnetic Resonance · doi:10.1016/j.ssnmr.2017.08.003 · Cited by 35
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Goedert, M., Yamaguchi, Y., Mishra, S. K., Higuchi, M., & Sahara, N. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00070 · Cited by 32
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de Rooij, R., & Ellen Kuhl, A. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00144 · Cited by 32
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Mondal, S., Jacoby, G., Sawaya, M. R., Arnon, Z. A., Adler‐Abramovich, L., Rehak, P. L., Vuković, L., Shimon, L. J. W., Král, P., Beck, R., et al. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b10289 · Cited by 32
Prion-like properties of Tau assemblies
Clavaguera, F., Duyckaerts, C. J., & Haı̈k, S. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2019.11.022 · Cited by 32
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Lauretti, E., & Praticò, D. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1737012 · Cited by 34
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BackgroundHeterotypic interactions in amyloid function and disease
Konstantoulea, K., Louros, N. N., Rousseau, F., & Schymkowitz, J. W. H. (2021) · FEBS Journal · doi:10.1111/febs.15719 · Cited by 34
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Lewkowicz, E., Jayaraman, S., & Gursky, O. (2021) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2021.05.003 · Cited by 32
Three‐repeat and four‐repeat tau isoforms form different oligomers
Shahpasand‐Kroner, H., Portillo, J., Lantz, C., Seidler, P. M., Sarafian, N., Loo, J. A., & Bitan, G. (2021) · Protein Science · doi:10.1002/pro.4257 · Cited by 32
Li, X., Zhang, S., Liu, Z., Tao, Y., Xia, W., Sun, Y., Liu, C., Le, W., Sun, B., & Li, D. (2022) · iScience · doi:10.1016/j.isci.2022.105645 · Cited by 32
Chukwu, J. E., Pedersen, J. T., Pedersen, L. Ø., Volbracht, C., Sigurdsson, E. M., & Kong, X. (2018) · Scientific Reports · doi:10.1038/s41598-018-24276-4 · Cited by 32
Jia, B., Shen, Z., Zhu, S., Huang, J., Liao, Z., Zhao, S., Li, H., Chen, S., Xu, Y., Wang, Y., et al. (2025) · Cell · doi:10.1016/j.cell.2025.07.047 · Cited by 25
Tau fibrils evade autophagy by excessive p62 coating and TAX1BP1 exclusion
Ferrari, L., Bauer, B., Qiu, Y., Schuschnig, M., Klotz, S., Anrather, D., Juretschke, T., Beli, P., Gelpí, E., & Martens, S. (2024) · Science Advances · doi:10.1126/sciadv.adm8449 · Cited by 35
Ligand-based design of [18F]OXD-2314 for PET imaging in non-Alzheimer’s disease tauopathies
Lindberg, A., Murrell, E., Tong, J., Mason, N. S., Sohn, D., Sandell, J., Ström, P., Stehouwer, J. S., Lopresti, B. J., Viklund, J., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-49258-1 · Cited by 32
Buchanan, L. E., Maj, M., Dunkelberger, E. B., Cheng, P.-N., Nowick, J. S., & Zanni, M. T. (2018) · Biochemistry · doi:10.1021/acs.biochem.8b00997 · Cited by 31
In-Cell NMR Study of Tau and MARK2 Phosphorylated Tau
Zhang, S., Wang, C., Lu, J., Ma, X., Liu, Z., Li, D., Liu, Z., & Liu, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms20010090 · Cited by 31
“These filamentous aggregates are the pathological hallmarks of a variety of neurodegenerative diseases including Alzheimer’s disease (AD) [36], Pick’s disease [37], and progressive supranuclear palsy [38].”
BackgroundHyperpolarized MAS NMR of unfolded and misfolded proteins
König, A., Schölzel, D., Uluca, B., Viennet, T., Akbey, Ü., & Heise, H. (2019) · Solid State Nuclear Magnetic Resonance · doi:10.1016/j.ssnmr.2018.12.003 · Cited by 31
Kyrilis, F. L., Meister, A., & Kastritis, P. L. (2019) · Biological Chemistry · doi:10.1515/hsz-2018-0445 · Cited by 31
A Possible Neurodegeneration Mechanism Triggered by Diabetes
Farhadi, A., Vosough, M., Zhang, J., Tahamtani, Y., & Shahpasand, K. (2019) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2019.07.012 · Cited by 30
Balasubramaniam, M., Ayyadevara, S., Ganne, A., Kakraba, S., Penthala, N. R., Du, X., Crooks, P. A., Griffin, S. T., & Reis, R. J. S. (2019) · iScience · doi:10.1016/j.isci.2019.09.026 · Cited by 28
ATP Kinetically Modulates Pathogenic Tau Fibrillations
Han, J. Y., Heo, C. E., Lim, S., Lee, J., Martsishevska, I., Im, D., Lee, M. J., Kim, H. I., & Kim, H. I. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00479 · Cited by 32
G protein‐coupled receptor kinases are associated with Alzheimer's disease pathology
Guimarães, T. R., Swanson, E., Kofler, J., & Thathiah, A. (2021) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12742 · Cited by 31
“However, as tau begins to form insoluble fibrillar filaments, many phosphorylation-specific epitopes become hidden in the fibril core [83, 84].”
BackgroundTranscellular Spreading of Tau in Tauopathies
Demaegd, K. C., Schymkowitz, J. W. H., & Rousseau, F. (2018) · ChemBioChem · doi:10.1002/cbic.201800288 · Cited by 32
Aggidis, A., Devitt, G., Zhang, Y., Chatterjee, S., Townsend, D. J., Fullwood, N. J., Ruiz, E., Tarutani, A., Hasegawa, M., Cooper, A. S., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14246 · Cited by 31
How short peptides disassemble tau fibrils in Alzheimer’s disease
Hou, K., Ge, P., Sawaya, M. R., Lutter, L., Dolinsky, J. L., Yang, Y., Jiang, Y. X., Boyer, D. R., Cheng, X., Pi, J., et al. (2025) · Nature · doi:10.1038/s41586-025-09244-z · Cited by 30
“Owing to their mock-amyloid nature, D-TLKIVWX protofilaments extend from the nuclei, but are constrained to adopt the left-handed helical twist of AD-tau PHFs, as in the cryo-trapped structure in Fig.”
InfluentialModeling the Axon as an Active Partner with the Growth Cone in Axonal Elongation
de Rooij, R., Ellen Kuhl, A., & Miller, K. E. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2018.08.047 · Cited by 28
Jiang, L., Zhao, J., Cheng, J., & Wolozin, B. L. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.579434 · Cited by 31
Leonard, C., Phillips, C., & McCarty, J. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.624302 · Cited by 30
“Recent high-resolution cryo-EM structures of the tau fibril core, isolated from the brain of an individual with AD, reveal the detailed C-shaped core structure formed by residues 306–378 that are part of the R3-R4 repeat domain (Fitzpatrick et al., 2017).”
BackgroundCitrullination of Amyloid-β Peptides in Alzheimer’s Disease
Mukherjee, S., Perez, K. A., Dubois, C., Nisbet, R. M., Li, Q., Varghese, S., Jin, L., Birchall, I. E., Streltsov, V. A., Vella, L. J., et al. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00474 · Cited by 30
Cryo-EM structures of τ filaments from human brain
Goedert, M. (2021) · Essays in Biochemistry · doi:10.1042/ebc20210025 · Cited by 33
Self-citationBased on molecular structures: Amyloid-β generation, clearance, toxicity and therapeutic strategies
Yang, H., Li, J., Li, X., Ma, L., Hou, M., Zhou, H., & Zhou, R. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.927530 · Cited by 33
Zou, Y. F., Qi, B., Tan, J., Sun, Y., Gong, Y., & Zhang, Q. (2022) · Physical Chemistry Chemical Physics · doi:10.1039/d2cp02353a · Cited by 30
Riedel, G., Klein, J., Niewiadomska, G., Kondak, C., Schwab, K., Lauer, D., Magbagbeolu, M., Steczkowska, M., Zadrożny, M., Wydrych, M., et al. (2020) · Current Alzheimer Research · doi:10.2174/1567205017666200224120926 · Cited by 31
Alzheimer’s disease seeded tau forms paired helical filaments yet lacks seeding potential
Duan, P., Dregni, A. J., Xu, H. W., Changolkar, L. N., Lee, V. M. ‐., Lee, E. B., & Hong, M. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.107730 · Cited by 36
Shen, X., Li, H., Zhang, B., Li, Y., & Zhu, Z. (2025) · Cells · doi:10.3390/cells14191506 · Cited by 33
“These dimensions dictate which epitopes are exposed, which species can be neutralised in vivo, and which therapeutic approaches, such as antibodies, oncogenes, or vaccines, are most likely to bind to disease-associated tau [35,36].”
The potential of cryo-electron microscopy for structure-based drug design
Boland, A., Chang, L., & Barford, D. (2017) · Essays in Biochemistry · doi:10.1042/ebc20170032 · Cited by 32
Metadata
- Authors
- Fitzpatrick, A. W. P., Falcon, B., He, S., Murzin, A. G., Murshudov, G., Garringer, H. J., Crowther, R. A., Ghetti, B., Goedert, M., & Scheres, S. H. W.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Indiana University Indianapolis (US)
- Corresponding author
- Goedert, Michel
- Scheres, Sjors H. W.
- ORCID
- Venue
- Nature
- Published
- 2017-07
- Volume
- 547
- Issue
- 7662
- Pages
- 185-190
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5552202
- OpenAlex
- W2727929522
- Cited by
- 2,061
- References
- 58
- Citations by year
- 2026: 197 · 2025: 224 · 2024: 225 · 2023: 224 · 2022: 214 · 2021: 231 · 2020: 280 · 2019: 227 · 2018: 193 · 2017: 42
- FWCI
- 150.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- PMC
- Funders
- Medical Research Council (MC_EX_MR/N027892/1)
- National Institute on Aging (P30AG010133)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, tau filaments, paired helical filaments, straight filaments, tau aggregation, protofilaments, tauopathy, neurodegenerative diseases
- MeSH terms
- Aged, Alzheimer Disease, Amino Acid Sequence, Amyloid, Brain, Female, Humans, tau Proteins, Cryoelectron Microscopy, Protein Aggregation, Pathological
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