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 901–1,000 of 1,003
Protein aggregation and neurodegenerative disease: Structural outlook for the novel therapeutics
Arar, S. H., Haque, M. A., & Kayed, R. (2023) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26561 · Cited by 20
“Finally, all these techniques discussed here will provide the awaited structural information about the heterogeneous toxic protein aggregates in AD, 62 allow to mimic cytotoxic species in vivo or patient-derived material, 23,63 accelerating the designing of small molecules and production of more effective disease-modi…”
InfluentialSite‐Specific Ubiquitination of Tau Amyloids Promoted by the E3 Ligase CHIP
Parolini, F., Kachoie, E. A., Leo, G., Civiero, L., Bubacco, L., Arrigoni, G., Munari, F., Assfalg, M., D’Onofrio, M., & Capaldi, S. (2023) · Angewandte Chemie International Edition · doi:10.1002/anie.202310230 · Cited by 18
Broadening Horizons: Exploring the Cathepsin Family as Therapeutic Targets for Alzheimer's Disease
Liu, X., Liu, X., Wu, Y., Li, S., Ren, K., Cheng, M., Huang, B., Yang, Y., & Liu, P. (2024) · Aging and Disease · doi:10.14336/ad.2024.0456 · Cited by 20
Hoq, M. R., Fernández, A., Vago, F. S., Hallinan, G. I., Bharath, S. R., Li, D., Ozcan, K. A., Garringer, H. J., Jiang, W., Vidal, R., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02786-y · Cited by 19
Self-citationPathological Involvement of Protein Phase Separation and Aggregation in Neurodegenerative Diseases
Wu, Y.-F., Ma, B., Liu, C. Y., Li, D., & Sui, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251810187 · Cited by 21
“For example, the cryo-EM structures of tau filaments from AD individuals indicated that the paired helical and straight tau filaments, which account for neurofibrillary lesions, had the same protofilaments but their inter-protofilament packing was different [239].”
BackgroundFang, G., Shi, B., Wu, K., Chen, S., Gao, X., Xiao, S., Kang, J. X., Li, W., & Huang, R. (2018) · International Journal of Neuroscience · doi:10.1080/00207454.2018.1533824 · Cited by 19
“patients using cryo-electron microscopy (cryo-EM) [15].”
Lecoq, L., Wiegand, T., Rodríguez, F. J. Á., Cadalbert, R., Herrera, G. A., del Pozo‐Yauner, L., Meier, B. H., & Böckmann, A. (2018) · ChemBioChem · doi:10.1002/cbic.201800732 · Cited by 19
Barracchia, C. G., Tira, R., Parolini, F., Munari, F., Bubacco, L., Spyroulias, G. A., D’Onofrio, M., & Assfalg, M. (2020) · Molecules · doi:10.3390/molecules25112716 · Cited by 19
“Recent cryo-electron microscopy developments, which have begun to shed light onto the diversity of the filamentous assemblies of Tau with unprecedented resolution [18,58], could clarify whether FA-induced filaments morphologically resemble those found associated with distinct tauopathies.”
BackgroundWan, J., Gong, Y., Xu, Z., Dong, X., Wei, G., & Zhang, Q. (2021) · Biophysical Chemistry · doi:10.1016/j.bpc.2021.106541 · Cited by 19
Xu, X., Wang, Y., Zong, L., Chen, Z.-Y., & Li, Y. (2018) · Brain Research · doi:10.1016/j.brainres.2018.05.024 · Cited by 19
Foote, A. K., Manger, L. H., Holden, M. R., Margittai, M., & Goldsmith, R. H. (2018) · Physical Chemistry Chemical Physics · doi:10.1039/c8cp06971a · Cited by 19
The Structural Basis of Amyloid Strains in Alzheimer’s Disease
Makowski, L. (2019) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.9b01302 · Cited by 19
Novel tau filament fold in corticobasal degeneration, a four-repeat tauopathyPreprint
Zhang, W., Tarutani, A., Newell, K. L., Murzin, A. G., Matsubara, T., Falcon, B., Vidal, R., Garringer, H. J., Shi, Y., Ikeuchi, T., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/811703 · Cited by 19
Self-citationAdvances in PET imaging of protein aggregates associated with neurodegenerative disease
Higuchi, M., Tagai, K., Takahata, K., & Endo, H. (2025) · Nature Reviews Neurology · doi:10.1038/s41582-025-01126-2 · Cited by 21
Tracer development for PET imaging of proteinopathies
Kallinen, A., & Kassiou, M. (2022) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2022.04.001 · Cited by 18
Structural Mimicry in Microbial and Antimicrobial Amyloids
Golan, N., Engelberg, Y., & Landau, M. (2022) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-032620-105157 · Cited by 21
Aβ and Tau Prions Causing Alzheimer’s Disease
Condello, C., Merz, G. E., Aoyagi, A., DeGrado, W. F., & Prusiner, S. B. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2655-9_16 · Cited by 18
Trivellato, D., Floriani, F., Barracchia, C. G., Munari, F., D’Onofrio, M., & Assfalg, M. (2023) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.106347 · Cited by 18
Mutation ∆K281 in MAPT causes Pick’s disease
Schweighauser, M., Garringer, H. J., Klingstedt, T., Nilsson, K. P. R., Masuda‐Suzukake, M., Murrell, J. R., Risacher, S. L., Vidal, R., Scheres, S. H. W., Goedert, M., et al. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02598-6 · Cited by 18
“HS-84 interacts with regularly spaced lysine residues in grooves along amyloid filaments [27], whereas the most favourable ligand–protein interaction for bTVBT4 occurs at the hydrophobic pocket defined by I360, T361 and H362 in the Alzheimer Tau fold [16, 56].”
BackgroundSelf-citationEspresso Coffee Mitigates the Aggregation and Condensation of Alzheimer′s Associated Tau Protein
Tira, R., Viola, G., Barracchia, C. G., Parolini, F., Munari, F., Capaldi, S., Assfalg, M., & D’Onofrio, M. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c01072 · Cited by 18
Alzheimer proteopathic tau seeds are biochemically a forme fruste of mature paired helical filaments
Kumar, M., Quittot, N., Dujardin, S., Schlaffner, C. N., Viodé, A., Wiedmer, A. E., Beerepoot, P., Chun, J. E., Glynn, C. A., Fernandes, A. R., et al. (2024) · Brain · doi:10.1093/brain/awad378 · Cited by 20
Luca, W., Foster, K., McClure, K., Ahlijanian, M. K., & Jefson, M. R. (2024) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2024.25 · Cited by 18
Macrocyclic peptides derived from AcPHF6* and AcPHF6 to selectively modulate the Tau aggregation
Dangi, A., Qureshi, T., Chinnathambi, S., & Marelli, U. K. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107625 · Cited by 18
Methods for Structural Analysis of Amyloid Fibrils in Misfolding Diseases
Vadukul, D. M., Al‐Hilaly, Y. K., & Serpell, L. C. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-8820-4_7 · Cited by 17
Intrinsically disordered proteins (IDPs) studied by EPR and in-cell EPR
Weickert, S., Cattani, J., & Drescher, M. (2018) · Royal Society of Chemistry eBooks · doi:10.1039/9781788013888-00001 · Cited by 18
Cao, Y., Tang, X. L., Miao, Y., & Han, W. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.12.008 · Cited by 18
Giampà, M., & Sgobba, E. (2020) · Molecules · doi:10.3390/molecules25214979 · Cited by 19
Determination of the 3D Atomic Structures of Nanoparticles
Kim, B. H., Heo, J., & Park, J. (2020) · Small Science · doi:10.1002/smsc.202000045 · Cited by 18
In Silico Modeling of the Influence of Environment on Amyloid Folding Using FOD-M Model
Roterman, I., Stąpor, K., Fabian, P., & Konieczny, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910587 · Cited by 18
“An exception to the proposed model and interpretation is the example of the tau protein [43], whose partial characterization (native form is not available) suggests the scenario proposed for the transthyretin and V domain of the IgG light chain.”
BackgroundNMR Studies of Tau Protein in Tauopathies
Kitoka, K., Škrabana, R., Gašparik, N., Hritz, J., & Jaudzems, K. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.761227 · Cited by 17
“The PDSD spectra also allowed to assign 13 amino acids of the R4 repeat, which was concluded to be a part of the rigid core, in line with the various fibril structure models from cryo-EM (Fitzpatrick et al., 2017; Falcon et al., 2018).”
BackgroundResultDNP-Assisted NMR Investigation of Proteins at Endogenous Levels in Cellular Milieu
Costello, W. N., Xiao, Y., & Frederick, K. K. (2018) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/bs.mie.2018.08.023 · Cited by 17
Improving Mouse Models for Dementia. Are All the Effects in Tau Mouse Models Due to Overexpression?Preprint
Joel, Z., Izquierdo, P., Salih, D. A. M., Richardson, J. C., Cummings, D. M., & Edwards, F. A. (2018) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2018.83.037531 · Cited by 18
“Further questions also arise considering the types of Tau that make up the different tangles and how these different forms of Tau would behave under normal and overexpression conditions (Fitzpatrick et al. 2017).”
BackgroundSeidler, P. M., Boyer, D. R., Sawaya, M. R., Ge, P., Shin, W., DeTure, M., Dickson, D. W., Jiang, L., & Eisenberg, D. S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.29.124537 · Cited by 18
Super-resolution microscopy for structural biology
Danial, J. S. H. (2025) · Nature Methods · doi:10.1038/s41592-025-02731-1 · Cited by 18
Molecular features of human pathological tau distinguish tauopathy-associated dementias
Kumar, M., Schlaffner, C. N., Tang, S., Beuvink, M. A., Viodé, A., Mair, W., Jha, M., Uncu, C., Wesseling, H., Wang, T., et al. (2026) · Cell · doi:10.1016/j.cell.2025.12.036 · Cited by 21
Tau Fibril Formation in Cultured Cells Compatible with a Mouse Model of Tauopathy
Matsumoto, G., Matsumoto, K., Kimura, T., Suhara, T., Higuchi, M., Sahara, N., & Mori, N. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051497 · Cited by 17
Iodine staining as a useful probe for distinguishing insulin amyloid polymorphs
Hiramatsu, T., Yamamoto, N., Ha, S., Masuda, Y., Yasuda, M., Ishigaki, M., Yuzu, K., Ozaki, Y., & Chatani, E. (2020) · Scientific Reports · doi:10.1038/s41598-020-73460-y · Cited by 17
Single Molecule Characterization of Amyloid Oligomers
Yang, J., Perrett, S., & Wu, S. (2021) · Molecules · doi:10.3390/molecules26040948 · Cited by 19
Lashley, T., Tossounian, M., Heaven, N. C., Wallworth, S., Peak‐Chew, S., Bradshaw, A., Cooper, J. A. D., de Silva, R., Srai, S. K., Malanchuk, O., et al. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.739425 · Cited by 19
Nguyen, P. H., & Derreumaux, P. (2022) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.2c02836 · Cited by 17
Targeting hIAPP fibrillation: A new paradigm to prevent β-cell death?
Guillemain, G., Lacapère, J.-J., & Khemtémourian, L. (2022) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2022.184002 · Cited by 18
Xing, J., Xian, H., Yang, Y., Chen, Q., Xi, J., Li, S., He, H., & Zhu, J. (2023) · ACS Earth and Space Chemistry · doi:10.1021/acsearthspacechem.2c00278 · Cited by 17
Peptide-based nanomaterials: Building back better & beyond
Conticello, V. P. (2023) · Current Opinion in Solid State and Materials Science · doi:10.1016/j.cossms.2023.101066 · Cited by 19
Probing differences among Aβ oligomers with two triangular trimers derived from Aβ
Kreutzer, A. G., Guaglianone, G., Yoo, S., Parrocha, C. M. T., Ruttenberg, S. M., Malonis, R. J., Tong, K., Lin, Y.-F., Nguyen, J. T., Howitz, W. J., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2219216120 · Cited by 18
Lipid‐induced polymorphic amyloid fibril formation by α‐synuclein
Singh, B., Morris, R. J., Kunath, T., MacPhee, C. E., & Horrocks, M. H. (2023) · Protein Science · doi:10.1002/pro.4736 · Cited by 15
Le, L., Lee, J., Im, D., Park, S., Hwang, K.-D., Lee, J., Jiang, Y., Lee, Y.-S., Suh, Y. H., Kim, H. I., et al. (2023) · Advancement of science · doi:10.1002/advs.202302035 · Cited by 13
Interaction of Proteins Involved in Neuronal Proteinopathies
Kulichikhin, K. Y., Malikova, O. A., Zobnina, A. E., Zalutskaya, N. M., & Rubel, A. A. (2023) · Life · doi:10.3390/life13101954 · Cited by 17
Ryder, B. D., Ustyantseva, E., Boyer, D. R., Mendoza‐Oliva, A., Kuska, M. I., Wydorski, P. M., Macierzyńska, P., Morgan, N., Sawaya, M. R., Diamond, M. I., et al. (2024) · Structure · doi:10.1016/j.str.2024.02.015 · Cited by 24
Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots
Kell, D. B., & Pretorius, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910809 · Cited by 17
“…must be parallels between the kinds of fibril formation that are seen in classical amyloidogenesis (commonly in the range 2–25 nm diameter [255,290–293]) and that seen in both normal and pathological blood clotting (although those fibrils are commonly at least 10x larger in diameter [198],…”
BackgroundConformational evolution of polymorphic amyloid assemblies
Chen, L., Hsieh, M.-C., Li, N. X., & Lynn, D. G. (2018) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2018.04.004 · Cited by 15
Tochio, N., Murata, T., & Utsunomiya‐Tate, N. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.11.043 · Cited by 17
Glutamine Side Chain 13C═18O as a Nonperturbative IR Probe of Amyloid Fibril Hydration and Assembly
Wu, H., Saltzberg, D. J., Kratochvil, H. T., Jo, H., Šali, A., & DeGrado, W. F. (2019) · Journal of the American Chemical Society · doi:10.1021/jacs.9b00577 · Cited by 17
Modulation of Innate Immunity by Amyloidogenic Peptides
Westwell-Roper, C. Y., & Verchere, C. B. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.06.005 · Cited by 17
Shin, W. S., Di, J., Murray, K. A., Sun, C., Li, B., Bitan, G., & Jiang, L. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00268 · Cited by 17
“When tau aggregates into insoluble fibrils, these fibrillar species can act as a seed to facilitate further conversion of tau monomers into the fibrillar form (Kfoury et al., 2012; Jackson et al., 2016; Fitzpatrick et al., 2017).”
BackgroundRetractedTryptophan–glucosamine conjugates modulate tau-derived PHF6 aggregation at low concentrations
Paul, A., Li, W., Viswanathan, G. K., Arad, E., Mohapatra, S., Gao, L., Jelinek, R., Gazit, E., Li, Y., & Segal, D. (2019) · Chemical Communications · doi:10.1039/c9cc06868f · Cited by 17
Banach, M., Konieczny, L., & Roterman, I. (2019) · Molecules · doi:10.3390/molecules24234395 · Cited by 17
“Aβ (15–40) 2MPZ 26 aa 15–40 D23N 56 9 × 3 [73] Aβ (11–42) 2MXU 32 aa 11–42 68 12 × 1 [74] Aβ (1–40) 2MVX 39aa 1–40 E22∆ 35 5 × 2 [73] Aβ (11–42) 5KK3 32 aa 11–42 59 9 × 2 [75] TAU 5O3L 73 aa 306–378 13 5 × 2 [76] 5O3O 73 aa 306–378 13 5 × 2 [77] 5O3T 73 aa 306–378 13 5 × 2 [78] ASyn 2N0A 140/70 aa* 1–140 * 92 10 × 1 […”
In Vivo Validation of a Small Molecule Inhibitor of Tau Self-Association in htau Mice
Davidowitz, E. J., Krishnamurthy, P., Lopez, P. L. D. C., Jimenez, H. T., Adrien, L. R., Davies, P., & Moe, J. G. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190465 · Cited by 18
Combining molecular dynamics simulations and experimental analyses in protein misfolding
Wille, H., Dorosh, L., Amidian, S., Schmitt‐Ulms, G., & Stepanova, M. (2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2019.10.001 · Cited by 17
Pourhamzeh, M., Joghataei, M. T., Mehrabi, S., Ahadi, R., Hojjati, S. M. M., Fazli, N., Nabavi, S. M., Pakdaman, H., & Shahpasand, K. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00906-2 · Cited by 18
RetractedSchiefecker, A. J., Putzer, G., Braun, P., Martini, J., Strapazzon, G., Antunes, A. P., Mulino, M., Pinggera, D., Glodny, B., Brugger, H., et al. (2020) · Therapeutic Hypothermia and Temperature Management · doi:10.1089/ther.2020.0016 · Cited by 17
Alyenbaawi, H., Allison, W. T., & Mok, S. (2020) · Biomolecules · doi:10.3390/biom10111487 · Cited by 20
“(B) In AD tau filaments, part of the tau repeat region (R3 and R4) forms the core of the filaments while R1, R2, and both N and C terminals form the “fuzzy coat” structure that surrounds the core (based on the Cryo-EM structure described in [58]).”
BackgroundInfluentialA theoretical study of polymorphism in VQIVYK fibrils
Yang, J., Agnihotri, M. V., Huseby, C. J., Kuret, J., & Singer, S. J. (2021) · Biophysical Journal · doi:10.1016/j.bpj.2021.01.032 · Cited by 17
“In this picture, the VQIVYK sheet acts like a vertical column of a tall building to which other architectural elements attach, and the bsheet partners opposing VQIVYK, e.g., THKLTF for Alzheimer’s disease, play a lesser role.”
BackgroundInfluentialCheng, K. H., Graf, A., Lewis, A., Pham, T. L. H., & Acharya, A. (2022) · Membranes · doi:10.3390/membranes12111098 · Cited by 17
“The creation of an all-atom (AA) 130-residue long Tau-K18 monomer was based on a cryoEM-derived, fibrillar tau pentamer structure [3] as shown in Figure 1A.”
Untangling the tauopathies: Current concepts of tau pathology and neurodegeneration
Ling, H. (2017) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2017.07.031 · Cited by 18
Detection of tau in Gerstmann-Sträussler-Scheinker disease (PRNP F198S) by [18F]Flortaucipir PET
Risacher, S. L., Farlow, M. R., Bateman, D. R., Epperson, F., Tallman, E. F., Richardson, R. M., Murrell, J. R., Unverzagt, F. W., Apostolova, L. G., Bonnin, J. M., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0608-z · Cited by 19
Self-citationAhmed, S., Díez-Fairén, M., Sabir, M. S., Pástor, P., Ding, J., Ispierto, L., Butala, A., Morris, C. M., Schulte, C., Gasser, T., et al. (2019) · Neurology Genetics · doi:10.1212/nxg.0000000000000347 · Cited by 18
“A previously described, cryo-electron microscopy structure of the tau protofibril was used for 3-dimensional protein modeling (figure 1).(23) Allele frequency differences between CBS cases and neurologically healthy Glossary”
Considerations for future tau-targeted therapeutics: can they deliver?
Noble, W. J., Jiménez-Sánchez, M., Perez‐Nievas, B. G., & Hanger, D. P. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2020.1685977 · Cited by 16
The big tau splice isoform resists Alzheimer’s-related pathological changesPreprint
Chung, D. C., Deng, X., Yalamanchili, H. K., Revelli, J., Han, A. L., Tadros, B., Richman, R., Dias, M., Naini, F. A., Boeynaems, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.30.605685 · Cited by 16
Mammeri, N. E., Duan, P., & Hong, M. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.4c13772 · Cited by 16
How is the Amyloid Fold Built? Polymorphism and the Microscopic Mechanisms of Fibril Assembly
Aubrey, L. D., & Radford, S. E. (2025) · Journal of Molecular Biology · doi:10.1016/j.jmb.2025.169008 · Cited by 19
Quantitative chemoproteomics reveals dopamine’s protective modification of Tau
Wang, Q., Liu, Z., Wang, Y. S., Liu, Y., Chen, Y., Zhang, S., Zeng, W., Li, D., Yang, F., He, Z., et al. (2025) · Nature Chemical Biology · doi:10.1038/s41589-025-01849-9 · Cited by 16
“Strikingly, in the structures of pathological hTau fibrils extracted from persons with AD and other tauopathies 43–49 , the two cysteines remain unmodified and are both involved in the fibril core formation in most of the hTau fibril structures (Extended Data Fig.”
The evolving role of solid state nuclear magnetic resonance methods in studies of amyloid fibrils
Tycko, R. (2025) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2025.103043 · Cited by 16
Water-directed pinning is key to tau prion formation
Vigers, M. P., Lobo, S., Najafi, S., DuBose, A., Tsay, K., Ganguly, P., Longhini, A. P., Jin, Y., Buratto, S. K., Kosik, K. S., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2421391122 · Cited by 24
Masuda‐Suzukake, M., Suzuki, G., Hosokawa, M., Nonaka, T., Goedert, M., & Hasegawa, M. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa091 · Cited by 16
Self-citationInteraction of Tau construct K18 with model lipid membranes
Azouz, M., Feuillie, C., Lafleur, M., Molinari, M., & Lecomte, S. (2021) · Nanoscale Advances · doi:10.1039/d1na00055a · Cited by 16
Cukkemane, A., Becker, N., Zielinski, M., Frieg, B., Lakomek, N., Heise, H., Schroeder, G. F., Willbold, D., & Weiergräber, O. H. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01765-1 · Cited by 14
“Amyloid systems, including PrP [53], Tau [54], and RIPK1-K3 [55] heteromers to name a few, have a small fraction of their sequences embedded in the β-core, while the remaining larger parts of the proteins often comprise dynamic regions.”
BackgroundRecent studies of atomic‐resolution structures of tau protein and structure‐based inhibitors
Zhu, L., & Qian, Z. (2021) · Quantitative Biology · doi:10.15302/j-qb-021-0271 · Cited by 16
APPsα Rescues Tau-Induced Synaptic Pathology
Bold, C. S., Baltissen, D., Ludewig, S., Back, M. K., Just, J., Kilian, L., Erdinger, S., Banićević, M., Rehra, L., Almouhanna, F., et al. (2022) · Journal of Neuroscience · doi:10.1523/jneurosci.2200-21.2022 · Cited by 17
Kimura, T., Ono, M., Seki, C., Sampei, K., Shimojo, M., Kawamura, K., Zhang, M., Sahara, N., Takado, Y., & Higuchi, M. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-05898-3 · Cited by 16
APPsα rescues CDK5 and GSK3β dysregulation and restores normal spine density in Tau transgenic mice
Baltissen, D., Bold, C. S., Rehra, L., Banićević, M., Fricke, J., Just, J., Ludewig, S., Buchholz, C. J., Körte, M., & Müller, U. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1106176 · Cited by 18
“This promotes its mislocalization to the somatodendritic compartment and a transition from soluble to insoluble oligomers that fibrillize and are finally deposited as NFTs (Fitzpatrick et al., 2017; Wegmann et al., 2018).”
BackgroundChiral and Structural Polymorphism of Fibril Architectures of Homologous Lysozymes
Hachlica, N., Rawski, M., Górecki, M., Wajda, A., & Kaczor, A. (2023) · Chemistry - A European Journal · doi:10.1002/chem.202203827 · Cited by 16
Tau, RNA, and RNA-Binding Proteins: Complex Interactions in Health and Neurodegenerative Diseases
Lester, E., & Parker, R. (2023) · The Neuroscientist · doi:10.1177/10738584231154551 · Cited by 16
Ondrejčák, T., Klyubin, I. V., Hu, N., O’Malley, T. T., Corbett, G. T., Winters, R., Perkinton, M. S., Billinton, A., Prenderville, J. A., Walsh, D. M., et al. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0082-23.2023 · Cited by 17
Distinct tau folds initiate templated seeding and alter the post-translational modification profile
Tarutani, A., Kametani, F., Tahira, M., Saito, Y., Yoshida, M., Robinson, A., Mann, D. M. A., Murayama, S., Tomita, T., & Hasegawa, M. (2023) · Brain · doi:10.1093/brain/awad272 · Cited by 18
Organic chiral nano- and microfilaments: types, formation, and template applications
Gowda, A., Pathak, S. K., Rohaley, G. A. R., Acharjee, G., Oprandi, A., Williams, R., Prévôt, M. E., & Hegmann, T. (2023) · Materials Horizons · doi:10.1039/d3mh01390a · Cited by 17
Emerging Trends in Cryo-EM-based Structural Studies of Neuropathological Amyloids
Mishra, S. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168361 · Cited by 16
Pinzi, L., Conze, C., Bisi, N., Torre, G. D., Soliman, A., Monteiro-Abreu, N., Trushina, N. I., Krusenbaum, A., Dolouei, M. K., Hellwig, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-45851-6 · Cited by 17
Engineered Antibodies to Improve Efficacy against Neurodegenerative Disorders
Niazi, S. K., Mariam, Z., & Magoola, M. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126683 · Cited by 16
“Moreover, it is 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) [76,77].”
BackgroundHou, G., Li, Y., Cui, X., Zhao, B., Liu, L., Zhang, Y., Yuan, H., & Zhang, L. (2024) · Analytical Chemistry · doi:10.1021/acs.analchem.4c02807 · Cited by 16
Rejc, L., Šmid, L. M., Kepe, V., Podlipnik, Č., Golobič, A., Bresjanac, M., Barrio, J. R., Petrič, A., & Košmrlj, J. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00764 · Cited by 16
Shedding light on aberrant interactions – a review of modern tools for studying protein aggregates
Kundel, F., Tosatto, L., Whiten, D. R., Wirthensohn, D. C., Horrocks, M. H., & Klenerman, D. (2018) · FEBS Journal · doi:10.1111/febs.14409 · Cited by 16
Novel monoclonal antibodies targeting the microtubule-binding domain of human tau
Croft, C. L., Moore, B. D., Ran, Y., Chakrabarty, P., Levites, Y., Golde, T. E., & Giasson, B. I. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195211 · Cited by 16
Electron cryomicroscopy as a powerful tool in biomedical research
Quentin, D., & Raunser, S. (2018) · Journal of Molecular Medicine · doi:10.1007/s00109-018-1640-y · Cited by 16
Expression and purification of amyloid β-protein, tau, and α-synuclein in Escherichia coli: a review
Jia, L., Zhao, W., Wei, W., Guo, X. L., Wang, W., Wang, Y., Sang, J., Lu, F., & Liu, F. (2020) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2020.1742646 · Cited by 16
“It was reported that the filament core of tau contained two identical protofilaments comprising residues 306–378, which presents a C-shaped crossb/b-helix structure and defines the seed for tau aggregation [52].”
BackgroundInfluentialStructural strains of misfolded tau protein define different diseases
Stahlberg, H., & Riek, R. (2021) · Nature · doi:10.1038/d41586-021-02611-6 · Cited by 16
Protein Microgels from Amyloid Fibril Networks
Roode, L. W. Y., Shimanovich, U., Wu, S., Perrett, S., & Knowles, T. P. J. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-9791-2_7 · Cited by 16
Arbaciauskaite, M., Yu, L., & Cho, Y. K. (2021) · Antibody Therapeutics · doi:10.1093/abt/tbab004 · Cited by 16
“These tangles consist of paired helical filaments (PHFs) of microtubule-associated protein tau [1,2].”
BackgroundMorderer, D., Wren, M. C., Liu, F., Kouri, N., Maistrenko, A., Khalil, B., Pobitzer, N., Salemi, M., Phinney, B. S., Bu, G., et al. (2025) · Molecular Neurodegeneration · doi:10.1186/s13024-025-00817-0 · Cited by 21
Murray, M. E., Smith, C., Menon, V., Keene, C. D., Lein, E. S., Hawrylycz, M., Aguzzi, A., Benedetti, B. L., Brose, K., Caetano-Anollés, K., et al. (2025) · Neuron · doi:10.1016/j.neuron.2025.06.014 · Cited by 16
Simonetti, F., Zhong, W., Hutten, S., Uliana, F., Schifferer, M., Rezaei, A., Ramirez, L. M., Hochmair, J., Sankar, R., Gopalan, A. B., et al. (2025) · The EMBO Journal · doi:10.1038/s44318-025-00590-2 · Cited by 22
“5), we speculate that TDP-43 under these experimental conditions may bind to the proto fi lament core region of Tau (~306 – 378 aa) (Fitzpatrick et al, 2017; Oakley et al, 2020).”
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
