The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
The cited source says what the claim attributes to it.
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Items 201–300 of 1,003
Ulamec, S. M., Brockwell, D. J., & Radford, S. E. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.611285 · Cited by 106
Kreutzer, A. G., & Nowick, J. S. (2018) · Accounts of Chemical Research · doi:10.1021/acs.accounts.7b00554 · Cited by 108
Biomolecular Assemblies: Moving from Observation to Predictive Design
Wilson, C. J., Bommarius, A. S., Champion, J. A., Chernoff, Y. O., Lynn, D. G., Paravastu, A. K., Chen, L., Hsieh, M.-C., & Heemstra, J. M. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00038 · Cited by 108
Perov, S., Lidor, O., Salinas, N., Golan, N., Tayeb-Fligelman, E., Deshmukh, M. G., Willbold, D., & Landau, M. (2019) · PLoS Pathogens · doi:10.1371/journal.ppat.1007978 · Cited by 111
Hashemi, M., Zandieh, M. A., Talebi, Y., Rahmanian, P., Shafiee, S. S., Nejad, M. M., Babaei, R., Sadi, F. H., Rajabi, R., Abkenar, Z. O., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114392 · Cited by 117
RetractedLemoine, L., Gillberg, P.-G., Svedberg, M. M., Stepanov, V. A., Jia, Z., Huang, J., Nag, S., Tian, H., Ghetti, B. F., Okamura, N., et al. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0325-z · Cited by 113
Self-citationNew insights on the structure of alpha-synuclein fibrils using cryo-electron microscopy
Guerrero-Ferreira, R., Kováčik, Ľ., Ni, D., & Stahlberg, H. (2020) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2020.01.014 · Cited by 109
Tau interactome and RNA binding proteins in neurodegenerative diseases
Kavanagh, T., Halder, A., & Drummond, E. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00572-6 · Cited by 111
“For example, tau aggregates into straight or paired helical filaments in AD [3, 35].”
BackgroundHaj‐Yahya, M., Gopinath, P., Rajasekhar, K., Mirbaha, H., Diamond, M. I., & Lashuel, H. A. (2019) · Angewandte Chemie International Edition · doi:10.1002/anie.201913001 · Cited by 106
Insights into Disease-Associated Tau Impact on Mitochondria
Szabo, L., Eckert, A., & Grimm, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176344 · Cited by 107
“This transition from pre-tangles to PHFs includes the formation of characteristic β-sheet-like structures [11,73].”
BackgroundPET Neuroimaging of Alzheimer's Disease: Radiotracers and Their Utility in Clinical Research
Bao, W., Xie, F., Zuo, C., Guan, Y., & Huang, Y. H. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.624330 · Cited by 102
The cellular model for Alzheimer's disease research: PC12 cells
Xie, D., Deng, T., Zhai, Z., Sun, T., & Xu, Y. D. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1016559 · Cited by 107
“The cerebral cortex of AD patients appear abundant neurofibrillary lesions and neuritic plaques (Fitzpatrick et al., 2017).”
BackgroundDancing with the Diva: Hsp90–Client Interactions
Radli, M., & Rüdiger, S. (2018) · Journal of Molecular Biology · doi:10.1016/j.jmb.2018.05.026 · Cited by 101
“The two C-terminal repeats R3 (V306–Q336) and R4 (V337–N368) are part of the fibrils found Alzheimer brain (V306–F378) [54].”
BackgroundDregni, A. J., Mandala, V. S., Wu, H., Elkins, M. R., Wang, H. K., Hung, I., DeGrado, W. F., & Hong, M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1906839116 · Cited by 98
“However, a recent cryo-EM study reported that heparin-fibrillized 2N4R tau exhibits at least 4 molecular structures (14): The dominant polymorph represents less than 45% of all fibrils and none of the structures are similar to the in vivo tau structures of AD or CTE (10, 15).”
BackgroundInfluentialNguyen, P. H., & Derreumaux, P. (2020) · Biophysical Chemistry · doi:10.1016/j.bpc.2020.106421 · Cited by 100
The 3D structure of lipidic fibrils of α-synuclein
Frieg, B., Antonschmidt, L., Dienemann, C., Geraets, J. A., Najbauer, E. E., Matthes, D., de Groot, B. L., Andreas, L. B., Becker, S., Griesinger, C., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34552-7 · Cited by 100
“In recent years, a growing number of ex vivo cryo-EM fibril structures have been discovered 5 that are characteristic of different diseases (29-31).”
BackgroundEmerging Structural Understanding of Amyloid Fibrils by Solid-State NMR
Meier, B. H., Riek, R., & Böckmann, A. (2017) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2017.08.001 · Cited by 101
Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy
Bonomi, M., Pellarin, R., & Vendruscolo, M. (2018) · Biophysical Journal · doi:10.1016/j.bpj.2018.02.028 · Cited by 99
Stress as risk factor for Alzheimer’s disease
Caruso, A., Nicoletti, F., Mango, D., Saidi, A., Orlando, R., & Scaccianoce, S. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.04.017 · Cited by 101
Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates
Gyparaki, M. T., Arab, A., Sorokina, E. M., Santiago-Ruiz, A. N., Bohrer, C. H., Xiao, J., & Lakadamyali, M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2021461118 · Cited by 97
“Recently, cryo-EM studies have also revealed the high-resolution structures of insoluble tau aggregates, including paired helical filaments (PHF) and straight filaments (SFs) from AD brain (8).”
BackgroundStability matters, too – the thermodynamics of amyloid fibril formation
Buell, A. K. (2022) · Chemical Science · doi:10.1039/d1sc06782f · Cited by 99
The mechanism of Hsp90-induced oligomerizaton of Tau
Weickert, S., Wawrzyniuk, M., John, L., Rüdiger, S., & Drescher, M. (2020) · Science Advances · doi:10.1126/sciadv.aax6999 · Cited by 98
“Positions probed in the experiment are also indicated on a schematic representation of the Tau sequence, with indicated Hsp90-binding site (25) and the core of the AD fibril (11), yellow and green stars indicating spin labeling positions without and with changes in eff upon addition of Hsp90, respectively.”
InfluentialAbskharon, R. N. N., Sawaya, M. R., Boyer, D. R., Cao, Q., Nguyen, B. A., Cascio, D., & Eisenberg, D. S. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2119952119 · Cited by 97
CSF tau microtubule-binding region identifies pathological changes in primary tauopathies
Horie, K., Barthélemy, N. R., Spina, S., VandeVrede, L. A., He, Y., Paterson, R. W., Wright, B. A., Day, G. S., Davis, A. A., Karch, C. M. M., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-02075-9 · Cited by 99
Current Status of Clinical Trials on Tau Immunotherapies
Ji, C., & Sigurdsson, E. M. (2021) · Drugs · doi:10.1007/s40265-021-01546-6 · Cited by 96
Targeting tau: clinical trials and novel therapeutic approaches
VandeVrede, L., Boxer, A. L., & Polydoro, M. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134919 · Cited by 90
Uematsu, M., Nakamura, A., Ebashi, M., Hirokawa, K., Takahashi, R., & Uchihara, T. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0501-1 · Cited by 96
Computational Studies Applied to Flavonoids against Alzheimer’s and Parkinson’s Diseases
Monteiro, A., Viana, J. D. O., Nayarisseri, A., Ernestine, N., Mendonça, F. J. B., Scotti, M. T., & Scotti, L. (2018) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2018/7912765 · Cited by 101
Propagation of Tau Pathology: Integrating Insights From Postmortem and In Vivo Studies
Vogels, T., Leuzy, A., Cicognola, C., Ashton, N. J., Smolek, T., Novák, M., Blennow, K., Zetterberg, H., Hromádka, T., Žilka, N., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.09.019 · Cited by 99
“306 to 378 and that the configurations of paired helical filaments and straight filaments are slightly different (83).”
Lin, Y., Fichou, Y., Zeng, Z., Hu, N. Y., & Han, S. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00627 · Cited by 93
Cryo-EM structure of a human prion fibril with a hydrophobic, protease-resistant core
Glynn, C. A., Sawaya, M. R., Ge, P., Gallagher-Jones, M., Short, C., Bowman, R., Apostol, M. I., Zhou, Z. H., Eisenberg, D. S., & Rodríguez, J. A. (2020) · Nature Structural & Molecular Biology · doi:10.1038/s41594-020-0403-y · Cited by 96
Hierarchical chemical determination of amyloid polymorphs in neurodegenerative disease
Li, D., & Liu, C. (2021) · Nature Chemical Biology · doi:10.1038/s41589-020-00708-z · Cited by 97
Al‐Hilaly, Y. K., Pollack, S. J., Vadukul, D. M., Citossi, F., Rickard, J. E., Simpson, M. C., Storey, J. M. D., Harrington, C. R., Wischik, C. M., & Serpell, L. C. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.09.007 · Cited by 93
Shin, W. S., Di, J., Cao, Q., Li, B., Seidler, P. M., Murray, K. A., Bitan, G., & Jiang, L. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0541-9 · Cited by 98
[11C]MODAG-001—towards a PET tracer targeting α-synuclein aggregates
Kuebler, L., Buss, S., Leonov, A., Ryazanov, S., Schmidt, F., Maurer, A., Weckbecker, D., Landau, A. M., Lillethorup, T. P., Bleher, D., et al. (2020) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-020-05133-x · Cited by 95
Yang, Y., Zhang, W., Murzin, A. G., Schweighauser, M., Huang, M., Lövestam, S., Peak‐Chew, S., Saito, T., Saido, T. C., Macdonald, J. A., et al. (2023) · Acta Neuropathologica · doi:10.1007/s00401-022-02533-1 · Cited by 93
“Tau filaments from case AβPParc1 were identical to PHFs from sporadic and familial cases of AD [9, 10].”
Self-citationGibbons, G. S., Banks, R. A., Kim, B., Changolkar, L., Riddle, D. M., Leight, S. N., Irwin, D. J., Trojanowski, J. Q., & Lee, V. M. Y. (2018) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nly010 · Cited by 94
Reid, M. J., Beltran-Lobo, P., Johnson, L., Perez‐Nievas, B. G., & Noble, W. J. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.572850 · Cited by 98
“In AD, both paired helical and straight filaments contain identical protofilament cores comprising residues 306– 378 that define the aggregatory seed/core (15).”
BackgroundBaughman, H. E. R., Clouser, A. F., Klevit, R. E., & Nath, A. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.803411 · Cited by 97
Modulation of Amyloid States by Molecular ChaperonesPreprint
Wentink, A. S., Nussbaum-Krammer, C. I., & Bukau, B. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033969 · Cited by 93
“Larger amyloidogenic proteins such as tau and αsyn only partially bury their polypeptide sequence in the final amyloid core, exposing “fuzzy” coats of disordered overhang sequences (Vilar et al. 2008; Tuttle et al. 2016; Fitzpatrick et al. 2017; Guerrero-Ferreira et al. 2018).”
BackgroundHyperphosphorylation Renders Tau Prone to Aggregate and to Cause Cell Death
Liu, M., Sui, D., Dexheimer, T. S., Hovde, S., Deng, X., Wang, K., Lin, H. L., Hagar, H. C., Kweon, H. K., Kuo, N. S., et al. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02034-w · Cited by 98
Sub-ångström cryo-EM structure of a prion protofibril reveals a polar clasp
Gallagher-Jones, M., Glynn, C. A., Boyer, D. R., Martynowycz, M. W., Hernandez, E., Miao, J., Zee, C.-T., Novikova, I. V., Goldschmidt, L., McFarlane, H. T., et al. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-017-0018-0 · Cited by 93
Murugan, N. A., Nordberg, A., & Ågren, H. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00093 · Cited by 92
Wiersma, V. I., van Ziel, A. M., Vazquez‐Sanchez, S., Nölle, A., Berenjeno‐Correa, E., Bonaterra‐Pastra, A., Clavaguera, F., Tolnay, M., Musters, R. J. P., van Weering, J. R. T., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02046-4 · Cited by 88
“1 3 ten residues from the sequence that forms the filament core in AD and Pick’s disease patient brains [17, 19].”
BackgroundThe growth of amyloid fibrils: rates and mechanisms
Buell, A. K. (2019) · Biochemical Journal · doi:10.1042/bcj20160868 · Cited by 95
Brandt, R., Trushina, N. I., & Bakota, L. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.590059 · Cited by 97
Classification of diseases with accumulation of Tau protein
Kovács, G. G., Ghetti, B. F., & Goedert, M. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12792 · Cited by 92
Self-citationCalabrese, G., Molzahn, C. M., & Mayor, T. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102062 · Cited by 92
“Moreover, it is now also evident that there are different polymorphs for most amyloid fibrils in vitro and in vivo (polymorph is a term used to indicate the capacity of a polypeptide to generate fibrils with different structures) (12, 13).”
BackgroundSoeda, Y., Saito, M., Maeda, S., Ishida, K., Nakamura, A., Kojima, S., & Takashima, A. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-181001 · Cited by 84
Stern, A. M., Yang, Y., Jin, S., Yamashita, K., Meunier, A. L., Liu, W., Cai, Y., Ericsson, M., Liu, L., Goedert, M., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.04.007 · Cited by 91
Self-citation3D structure determination of amyloid fibrils using solid-state NMR spectroscopy
Loquet, A., Mammeri, N. E., Stanek, J., Berbon, M., Bardiaux, B., Pintacuda, G., & Habenstein, B. (2018) · Methods · doi:10.1016/j.ymeth.2018.03.014 · Cited by 90
The peptide hormone glucagon forms amyloid fibrils with two coexisting β-strand conformations
Gelenter, M. D., Smith, K. J., Liao, S.-Y., Mandala, V. S., Dregni, A. J., Lamm, M. S., Tian, Y. P., Xu, W., Pochan, D. J., Tucker, T. J., et al. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0238-6 · Cited by 90
The hereditary mutation G51D unlocks a distinct fibril strain transmissible to wild-type α-synuclein
Sun, Y., Long, H., Xia, W., Wang, K., Zhang, X., Sun, B., Cao, Q., Zhang, Y., Dai, B., Li, D., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26433-2 · Cited by 88
Cell spheroid creation by transcytotic intercellular gelation
Guo, J., Wang, F., Huang, Y., He, H., Tan, W., Yi, M., Egelman, E. H., & Xu, B. (2023) · Nature Nanotechnology · doi:10.1038/s41565-023-01401-7 · Cited by 90
Tau at the interface between neurodegeneration and neuroinflammation
Didonna, A. (2020) · Genes & Immunity · doi:10.1038/s41435-020-00113-5 · Cited by 82
Tau immunotherapies: Lessons learned, current status and future considerations
Sandusky-Beltran, L. A., & Sigurdsson, E. M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108104 · Cited by 90
Fichou, Y., Vigers, M., Goring, A. K., Eschmann, N. A., & Han, S. (2018) · Chemical Communications · doi:10.1039/c8cc01355a · Cited by 89
Microtubule structure by cryo-EM: snapshots of dynamic instability
Manka, S. W., & Moores, C. A. (2018) · Essays in Biochemistry · doi:10.1042/ebc20180031 · Cited by 92
AlphaFold and the amyloid landscape
Pinheiro, F., Santos, J., & Ventura, S. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167059 · Cited by 88
Liquid–liquid phase separation of Tau by self and complex coacervation
Najafi, S., Lin, Y., Longhini, A. P., Zhang, X., Delaney, K. T., Kosik, K. S., Fredrickson, G. H., Shea, J., & Han, S. (2021) · Protein Science · doi:10.1002/pro.4101 · Cited by 90
High-throughput cryo-EM structure determination of amyloids
Lövestam, S., & Scheres, S. H. W. (2022) · Faraday Discussions · doi:10.1039/d2fd00034b · Cited by 92
Self-citationTen Years of Tau-Targeted Immunotherapy: The Path Walked and the Roads Ahead
Novak, P., Kontsekova, E., Zilka, N., & Novak, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00798 · Cited by 87
Co-factor-free aggregation of tau into seeding-competent RNA-sequestering amyloid fibrils
Chakraborty, P., Rivière, G., Liu, S., de Opakua, A. I., Dervişoğlu, R., Hebestreit, A., Andreas, L. B., Vorberg, I. M., & Zweckstetter, M. (2021) · Nature Communications · doi:10.1038/s41467-021-24362-8 · Cited by 83
Thal, D. R., & Tomé, S. O. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.10.006 · Cited by 92
The AAA+ chaperone VCP disaggregates Tau fibrils and generates aggregate seeds in a cellular system
Saha, I., Yuste‐Checa, P., Padilha, M. D. S., Guo, Q., Körner, R., Holthusen, H., Trinkaus, V. A., Dudanova, I., Fernández‐Busnadiego, R., Baumeister, W. P., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36058-2 · Cited by 93
GSK3β phosphorylation catalyzes the aggregation of tau into Alzheimer’s disease-like filaments
Chakraborty, P., Ibáñez de Opakua, A., Purslow, J. A., Fromm, S. A., Chatterjee, D., Zachrdla, M., Zhuang, S., Puri, S., Wolozin, B., & Zweckstetter, M. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2414176121 · Cited by 96
“In brain - derived extracts from AD patients, filaments com prising only two C - shaped protofilaments of tau have so far been observed ( 33 , 36 ) ( Fig.”
Rai, H., Gupta, S., Kumar, S., Yang, J., Singh, S. K., Ran, C., & Modi, G. P. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01619 · Cited by 87
Microtubule-binding core of the tau protein
Mammeri, N. E., Dregni, A. J., Duan, P., Wang, H. K., & Hong, M. (2022) · Science Advances · doi:10.1126/sciadv.abo4459 · Cited by 88
Tauopathies: Deciphering Disease Mechanisms to Develop Effective Therapies
Silva, M. C., & Haggarty, S. J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21238948 · Cited by 89
“In light of the cryo-EM studies showing two predominant types of tau fibrils in the AD postmortem brain [91,141], it seems”
BackgroundInfluentialWalker, L. C. (2020) · Free Neuropathology · doi:10.17879/freeneuropathology-2020-3025 · Cited by 113
Al‐Hilaly, Y. K., Foster, B. E., Biasetti, L., Lutter, L., Pollack, S. J., Rickard, J. E., Storey, J. M. D., Harrington, C. R., Xue, W., Wischik, C. M., et al. (2019) · FEBS Letters · doi:10.1002/1873-3468.13675 · Cited by 86
Neuropathological assessment of the Alzheimer spectrum
Jellinger, K. A. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02232-9 · Cited by 85
Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent responses
Meng, J. X., Zhang, Y., Saman, D., Haider, A. M., De, S., Sang, J. C., Brown, K., Jiang, K., Humphrey, J., Julian, L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-30461-x · Cited by 84
Human iPSC 4R tauopathy model uncovers modifiers of tau propagation
Parra Bravo, C., Giani, A. M., Madero-Perez, J., Zhao, Z., Wan, Y., Samelson, A. J., Wong, M. Y., Evangelisti, A., Cordes, E., Fan, L., et al. (2024) · Cell · doi:10.1016/j.cell.2024.03.015 · Cited by 90
Bishof, I., Dammer, E. B., Duong, D. M., Kundinger, S. R., Gearing, M., Lah, J. J., Levey, A. I., & Seyfried, N. T. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.001747 · Cited by 80
“This is notable, as a recent study examining the physical structure of Tau filaments in ADbrain revealed an exposed BAD motif within the tertiary structure of Tau, composed of residues 338–358 in the microtubule-binding repeat domain (67).”
BackgroundTau can switch microtubule network organizations: from random networks to dynamic and stable bundles
Prezel, E., Elie, A., Delaroche, J., Stoppin-Mellet, V., Bosc, C., Serre, L., Fourest-Lieuvin, A., Andrieux, A., Vantard, M., & Arnal, I. (2018) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-06-0429 · Cited by 83
Sharma, A. M., Thomas, T. L., Woodard, D. R., Kashmer, O. M., & Diamond, M. I. (2018) · eLife · doi:10.7554/elife.37813 · Cited by 80
Dai, B., Zhong, T., Chen, Z.-X., Chen, W., Zhang, N., Liu, X., Wang, L., Chen, J., & Liang, Y. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101222 · Cited by 83
Sarraf, S., Sarraf, A., DeSouza, D. D., Anderson, J. A. E., Kabia, M., & The Alzheimer's Disease Neuroimagin, A. D. N. I. (2023) · Brain Sciences · doi:10.3390/brainsci13020260 · Cited by 85
“The shrinkage of the brain, the atrophy of the posterior cortical, brain tissue degradation in the right temporal, parietal and left frontal lobes, and ventricular expansion progress over time and interfere with patients’ language and memory abilities [5]–[7].”
BackgroundLu, J., Zhang, S., Ma, X., Jia, C., Liu, Z., Huang, C., Liu, C., & Li, D. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.012284 · Cited by 80
“Four microtubule-binding repeat domains (R1–R4) have been shown to mediate Tau fibril formation (30).”
BackgroundFyn Kinase Controls Tau Aggregation In Vivo
Briner, A., Götz, J., & Polanco, J. C. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108045 · Cited by 85
Current Understanding of the Structure, Stability and Dynamic Properties of Amyloid Fibrils
Chatani, E., Yuzu, K., Ohhashi, Y., & Goto, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094349 · Cited by 82
Overview of tau PET molecular imaging
Petersen, G. C., Roytman, M., Chiang, G. C.-Y., Li, Y., Gordon, M. L., & Franceschi, A. M. (2022) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001035 · Cited by 87
Global Structure of the Intrinsically Disordered Protein Tau Emerges from Its Local Structure
Stelzl, L. S., Pietrek, L. M., Holla, A., Oroz, J., Sikora, M., Köfinger, J., Schuler, B., Zweckstetter, M., & Hummer, G. (2022) · JACS Au · doi:10.1021/jacsau.1c00536 · Cited by 79
Quantitative Analysis of the Brain Ubiquitylome in Alzheimer's Disease
Abreha, M. H., Dammer, E. B., Ping, L., Zhang, T., Duong, D. M., Gearing, M., Lah, J. J., Levey, A. I., & Seyfried, N. T. (2018) · PROTEOMICS · doi:10.1002/pmic.201800108 · Cited by 82
Tau prion-like propagation: state of the art and current challenges
Dujardin, S., & Hyman, B. T. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-32-9358-8_23 · Cited by 84
The structure of a minimum amyloid fibril core formed by necroptosis-mediating RHIM of human RIPK3
Wu, X., Ma, Y., Zhao, K., Zhang, J., Sun, Y., Li, Y., Dong, X.-Q., Hu, H., Liu, J., Wang, J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2022933118 · Cited by 81
Structure-Based Peptide Inhibitor Design of Amyloid-β Aggregation
Lu, J., Cao, Q., Wang, C., Zheng, J., Luo, F., Xie, J., Li, Y., Ma, X., He, L., Eisenberg, D. S., et al. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00054 · Cited by 80
Seyedrazizadeh, S.-Z., Poosti, S., Nazari, A., Alikhani, M., Shekari, F., Pakdel, F., Shahpasand, K., Satarian, L., & Baharvand, H. (2020) · Stem Cell Research & Therapy · doi:10.1186/s13287-020-01702-x · Cited by 87
Current directions in tau research: Highlights from Tau 2020
Sexton, C. E., Snyder, H. M., Beher, D., Boxer, A. L., Brannelly, P., Brion, J., Buée, L., Cacace, A. M., Chételat, G., Citron, M., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12452 · Cited by 89
Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases
Ravalin, M., Theofilas, P., Basu, K., Opoku-Nsiah, K., Assimon, V. A., Medina-Cleghorn, D., Chen, Y., Bohn, M., Arkin, M. R., Grinberg, L. T., et al. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0322-6 · Cited by 80
Mueller, R. L., Combs, B., Alhadidy, M. M., Brady, S. T., Morfini, G. A., & Kanaan, N. M. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.647054 · Cited by 81
Wang, F., Gnewou, O. M., Solemanifar, A., Conticello, V. P., & Egelman, E. H. (2022) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00753 · Cited by 78
Danis, C., Dupré, E., Zejneli, O., Caillierez, R., Arrial, A., Bégard, S., Mortelecque, J., Eddarkaoui, S., Loyens, A., Cantrelle, F., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.009 · Cited by 75
Modeling late-onset Alzheimer’s disease neuropathology via direct neuronal reprogramming
Sun, Z., Kwon, J.-S., Ren, Y., Chen, S., Walker, C. K., Lu, X., Cates, K., Karahan, H., Sviben, S., Fitzpatrick, J. A. J., et al. (2024) · Science · doi:10.1126/science.adl2992 · Cited by 77
“S9A), the impairment of synaptic formation likely reflects the degenerative state of LOAD neurons.”
Peet, B. T., Spina, S., Mundada, N., & La Joie, R. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01101-x · Cited by 74
The Ubiquitin System in Alzheimer’s Disease
Harris, L. D., Jasem, S., & Licchesi, J. D. F. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-38266-7_8 · Cited by 79
Gomes, L. A., Uytterhoeven, V., Lopez-Sanmartin, D., Tomé, S. O., Tousseyn, T., Vandenberghe, R. R., Vandenbulcke, M., Arnim, C. A. F. V., Verstreken, P., & Thal, D. R. (2021) · Acta Neuropathologica · doi:10.1007/s00401-020-02251-6 · Cited by 77
Fluent molecular mixing of Tau isoforms in Alzheimer’s disease neurofibrillary tangles
Dregni, A. J., Duan, P., Xu, H. W., Changolkar, L. N., Mammeri, N. E., Lee, V. M. ‐., & Hong, M. (2022) · Nature Communications · doi:10.1038/s41467-022-30585-0 · Cited by 76
De novo designed protein inhibitors of amyloid aggregation and seeding
Murray, K. A., Hu, C. J., Griner, S. L., Pan, H., Bowler, J. T., Abskharon, R. N. N., Rosenberg, G. M., Cheng, X., Seidler, P. M., & Eisenberg, D. S. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2206240119 · Cited by 77
“, Atomic-resolution structure of a disease-relevant Aβ(1-42) amyloid fibril.”
BackgroundMethodInfluential
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
