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.
“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]
In AD, tau tangles contain a mixture of 3R- and 4R-tau isoforms to adopt an AD-characteristic topology.
“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]
In AD, tau filaments assume a cross-β/β-helical fold.
“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]
Misfolding and aberrant accumulation of Tau is a pathological hallmark of Alzheimer's disease.
“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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Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. D. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 27,510 · see citing works
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 14,671 · see citing works
Self-citation<i>MolProbity</i> : 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 · see citing works
MotionCor2 - anisotropic correction of beam-induced motion for improved cryo-electron microscopy
Zheng, S., Palovcak, E. J., Armache, J., Verba, K., Cheng, Y.-F., & Agard, D. (2017) · Nature Methods · doi:10.1038/nmeth.4193 · Cited by 7,678 · see citing works
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 6,435 · see citing works
Gctf: Real-time CTF determination and correction
Zhang, K. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.11.003 · Cited by 3,372 · see citing works
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 · see citing works
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 · see citing works
Common core structure of amyloid fibrils by synchrotron X-ray diffraction.
Sunde, M., Serpell, L., Bartlam, M., Fraser, P., Pepys, M., & Blake, C. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1348 · Cited by 1,666 · see citing works
Goedert, M., Spillantini, M. G., Cairns, N. J., & Crowther, R. A. (1992) · Neuron · doi:10.1016/0896-6273(92)90117-v · Cited by 1,114 · see citing works
Self-citationMolecular Structure of β-Amyloid Fibrils in Alzheimer’s Disease Brain Tissue
Lu, J., Qiang, W., Yau, W., Schwieters, C. D., Meredith, S. C., & Tycko, R. (2013) · Cell · doi:10.1016/j.cell.2013.08.035 · Cited by 1,087 · see citing works
von Bergen, M., Friedhoff, P., Biernat, J., Heberle, J., Mandelkow, E.-M., & Mandelkow, E. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5129 · Cited by 1,021 · see citing works
Paired Helical Filaments in Electron Microscopy of Alzheimer's Disease
KIDD, M. (1963) · Nature · doi:10.1038/197192b0 · Cited by 1,012 · see citing works
Chen, S., McMullan, G., Faruqi, A. R., Murshudov, G. N., Short, J. M., Scheres, S. H. W., & Henderson, R. A. (2013) · Ultramicroscopy · doi:10.1016/j.ultramic.2013.06.004 · Cited by 1,005 · see citing works
Self-citationAmyloid Fibrils of the HET-s(218–289) Prion Form a β Solenoid with a Triangular Hydrophobic Core
Wasmer, C., Lange, A., Melckebeke, H. V., Siemer, A. B., Riek, R., & Meier, B. H. (2008) · Science · doi:10.1126/science.1151839 · Cited by 998 · see citing works
Solid-state NMR structure of a pathogenic fibril of full-length human α-synuclein
Tuttle, M. D., Comellas, G., Nieuwkoop, A. J., Covell, D. J., Berthold, D. A., Kloepper, K. D., Courtney, J. M., Kim, J. K., Barclay, A. M., Kendall, A. K., et al. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3194 · Cited by 951 · see citing works
Wischik, C. M., Novak, M., Thøgersen, H. C., Edwards, P. C., Runswick, M. J., Jakes, R., Walker, J. E., Milstein, C., Roth, M., & Klug, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.12.4506 · Cited by 939 · see citing works
Atomic Resolution Structure of Monomorphic Aβ42 Amyloid Fibrils
Colvin, M. T., Silvers, R., Ni, Q. Z., Can, T. V., Sergeyev, I. V., Rosay, M., Donovan, K. J., Michael, B. C., Wall, J. S., Linse, S. S., et al. (2016) · Journal of the American Chemical Society · doi:10.1021/jacs.6b05129 · Cited by 812 · see citing works
Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril
Wälti, M. A., Ravotti, F., Arai, H., Glabe, C. G., Wall, J. S., Böckmann, A., Güntert, P., Meier, B. H., & Riek, R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600749113 · Cited by 810 · see citing works
Brain homogenates from human tauopathies induce tau inclusions in mouse brain
Clavaguera, F., Akatsu, H., Fraser, G. M., Crowther, R. A., Frank, S., Hench, J., Probst, A., Winkler, D. T., Reichwald, J., Staufenbiel, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1301175110 · Cited by 750 · see citing works
Self-citationDomains of tau Protein and Interactions with Microtubules
Gustke, N., Trinczek, B., Biernat, J., Mandelkow, E.-M., & Mandelkow, E. (1994) · Biochemistry · doi:10.1021/bi00198a017 · Cited by 655 · see citing works
Wilcock, G. K., & Esiri, M. M. (1982) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(82)90155-1 · Cited by 608 · see citing works
Structural characterization of the core of the paired helical filament of Alzheimer disease.
Wischik, C. M., Novák, M., Edwards, P. C., Klug, A., Tichelaar, W., & Crowther, R. A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.13.4884 · Cited by 597 · see citing works
Self-citationAtomic structure and hierarchical assembly of a cross-β amyloid fibril
Fitzpatrick, A. W. P., Debelouchina, G. T., Bayro, M. J., Clare, D. K., Caporini, M. A., Bajaj, V. S., Jaroniec, C. P., Wang, L., Ladizhansky, V., Müller, S. A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219476110 · Cited by 567 · see citing works
Self-citationHelical reconstruction in RELION
He, S., & Scheres, S. H. W. (2017) · Journal of Structural Biology · doi:10.1016/j.jsb.2017.02.003 · Cited by 563 · see citing works
Self-citationEvidence for assembly of prions with left-handed β-helices into trimers
Govaerts, C., Wille, H., Prusiner, S. B., & Cohen, F. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402254101 · Cited by 540 · see citing works
The activities of amyloids from a structural perspective
Riek, R., & Eisenberg, D. S. (2016) · Nature · doi:10.1038/nature20416 · Cited by 504 · see citing works
Kaufman, S. K., Sanders, D. W., Thomas, T. L., Ruchinskas, A. J., Vaquer-Alicea, J., Sharma, A. M., Miller, T. M., & Diamond, M. I. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.055 · Cited by 450 · see citing works
Ghetti, B. F., Oblak, A. L., Boeve, B. F., Johnson, K. A., Dickerson, B. C., & Goedert, M. (2014) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12213 · Cited by 440 · see citing works
Self-citationGuo, J. L., Narasimhan, S., Changolkar, L., He, Z., Stieber, A., Zhang, B., Gathagan, R. J., Iba, M., McBride, J. D., Trojanowski, J. Q., et al. (2016) · Journal of Experimental Medicine · doi:10.1084/jem.20160833 · Cited by 440 · see citing works
THE FINE STRUCTURE OF NEUROFIBRILLARY TANGLES IN ALZHEIMERʼS DISEASE
Terry, R. D. (1963) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-196310000-00005 · Cited by 403 · see citing works
The Structural Basis of Monoclonal Antibody Alz50's Selectivity for Alzheimer's Disease Pathology
Carmel, G., Mager, E. M., Binder, L. I., & Kuret, J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32789 · Cited by 402 · see citing works
Crick, F. H. C., & Rich, A. (1955) · Nature · doi:10.1038/176780a0 · Cited by 373 · see citing works
Straight and paired helical filaments in Alzheimer disease have a common structural unit.
Crowther, R. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.6.2288 · Cited by 354 · see citing works
Self-citationÅslund, A., Sigurdson, C. J., Klingstedt, T., Grathwohl, S. A., Bolmont, T., Dickstein, D. L., Glimsdal, E., Prokop, S., Lindgren, M., Konradsson, P., et al. (2009) · ACS Chemical Biology · doi:10.1021/cb900112v · Cited by 332 · see citing works
Like prions: the propagation of aggregated tau and α-synuclein in neurodegeneration
Goedert, M., Masuda-Suzukake, M., & Falcon, B. (2017) · Brain · doi:10.1093/brain/aww230 · Cited by 323 · see citing works
Self-citationBerriman, J. A., Serpell, L. C., Oberg, K. A., Fink, A. L., Goedert, M., & Crowther, R. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530287100 · Cited by 288 · see citing works
Self-citationConformation Determines the Seeding Potencies of Native and Recombinant Tau Aggregates
Falcon, B., Cavallini, A., Angers, R. C., Glover, S. J., Murray, T. K., Barnham, L., Jackson, S., O'Neill, M. J., Isaacs, A. M., Hutton, M. L., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.589309 · Cited by 252 · see citing works
Self-citationPeptide dimer structure in an Aβ(1–42) fibril visualized with cryo-EM
Schmidt, M., Rohou, A. L., Lasker, K., Yadav, J. K., Schiene‐Fischer, C., Fändrich, M., & Grigorieff, N. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1503455112 · Cited by 219 · see citing works
Cytosolic Fc receptor TRIM21 inhibits seeded tau aggregation
McEwan, W. A., Falcon, B., Vaysburd, M., Clift, D., Oblak, A. L., Ghetti, B., Goedert, M., & James, L. C. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607215114 · Cited by 201 · see citing works
Self-citationTaniguchi-Watanabe, S., Arai, T., Kametani, F., Nonaka, T., Masuda-Suzukake, M., Tarutani, A., Murayama, S., Saito, Y., Arima, K., Yoshida, M., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1503-3 · Cited by 200 · see citing works
An R5L τ mutation in a subject with a progressive supranuclear palsy phenotype
Poorkaj, P., Muma, N. A., Zhukareva, V. A., Cochran, E. J., Shannon, K. M., Hurtig, H. I., Koller, W. C., Bird, T. D., Trojanowski, J. Q., Lee, V. M. ‐., et al. (2002) · Annals of Neurology · doi:10.1002/ana.10340 · Cited by 196 · see citing works
Abnormal Tau-Containing Filaments in Neurodegenerative Diseases
Crowther, R. A., & Goedert, M. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4270 · Cited by 185 · see citing works
Self-citationIverson, T. M., Alber, B. E., Kisker, C., Ferry, J. G., & Rees, D. C. (2000) · Biochemistry · doi:10.1021/bi000204s · Cited by 177 · see citing works
Jackson, S. J., Kerridge, C., Cooper, J., Cavallini, A., Falcon, B., Cella, C. V., Landi, A., Szekeres, P. G., Murray, T. K., Ahmed, Z., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.3542-15.2016 · Cited by 153 · see citing works
Self-citationFolding of the Tau Protein on Microtubules
Kadavath, H., Jaremko, M., Jaremko, Ł., Biernat, J., Mandelkow, E., & Zweckstetter, M. (2015) · Angewandte Chemie International Edition · doi:10.1002/anie.201501714 · Cited by 153 · see citing works
β‐Rolls, β‐Helices, and Other β‐Solenoid Proteins
Kajava, A. V., & Steven, A. C. (2006) · Advances in Protein Chemistry · doi:10.1016/s0065-3233(06)73003-0 · Cited by 149 · see citing works
Late‐onset frontotemporal dementia with a novel exon 1 (Arg5His) tau gene mutation
Hayashi, S., Toyoshima, Y., Hasegawa, M., Umeda, Y., Wakabayashi, K., Tokiguchi, S., Iwatsubo, T., & Takahashi, H. (2002) · Annals of Neurology · doi:10.1002/ana.10163 · Cited by 149 · see citing works
Identification of 3‐ and 4‐repeat tau isoforms within the PHF in Alzheimer's disease.
Jakes, R., Novák, M., Davison, M., & Wischik, C. M. (1991) · The EMBO Journal · doi:10.1002/j.1460-2075.1991.tb07820.x · Cited by 149 · see citing works
Braak, H., & Tredici, K. D. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023630 · Cited by 129 · see citing works
Structure-based drug design identifies polythiophenes as antiprion compounds
Herrmann, U., Schütz, A. K., Shirani, H., Danzhi Huang, A., Saban, D. V., Nuvolone, M., Li, B., Ballmer, B., Åslund, A., Mason, J. J., et al. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aab1923 · Cited by 126 · see citing works
Reappraisal of the fine structure of Alzheimer's neurofibrillary tangles
Yagishita, S., Itoh, Y., Nan, W., & Amano, N. (1981) · Acta Neuropathologica · doi:10.1007/bf00687747 · Cited by 109 · see citing works
The tauopathy associated with mutation +3 in intron 10 of Tau: characterization of the MSTD family
Spina, S., Farlow, M. R., Unverzagt, F. W., Kareken, D. A., Murrell, J. R., Fraser, G. M., Epperson, F., Crowther, R. A., Spillantini, M. G., Goedert, M., et al. (2007) · Brain · doi:10.1093/brain/awm280 · Cited by 102 · see citing works
Self-citationThe Dynamic Structure of Filamentous Tau
Bibow, S., Mukrasch, M. D., Chinnathambi, S., Biernat, J., Griesinger, C., Mandelkow�, E., & Zweckstetter, M. (2011) · Angewandte Chemie International Edition · doi:10.1002/anie.201105493 · Cited by 94 · see citing works
Dan, A., Takahashi, M., Masuda‐Suzukake, M., Kametani, F., Nonaka, T., Kondo, H., Akiyama, H., Arai, T., Mann, D. M. A., Saito, Y., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-54 · Cited by 71 · see citing works
Tau Positron Emission Tomography ImagingPreprint
Kolb, H. C., & Andrés, J. I. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023721 · Cited by 38 · see citing works
Xie, C., Soeda, Y., Shinzaki, Y., In, Y., Tomoo, K., Ihara, Y., & Miyasaka, T. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13228 · Cited by 27 · see citing works
Flagged first, then by citations
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Sorted by citations
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & van der Flier, W. M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32205-4 · Cited by 5,465 · see citing works
The neuropathological diagnosis of Alzheimer's disease
DeTure, M. A., & Dickson, D. W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0333-5 · Cited by 3,329 · see citing works
“5 A using cryoelectron microscopy [57].”
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
“Recent cryo-EM structures of tau fibrils derived from brains of AD patients (Fitzpatrick et al., 2017) and other tauopathies have demonstrated unexpected insights into fibril structures, and confirm that synthetic tau fibrils assume a vastly different folded structure as compared to AD brain-derived tau fibrils (for r…”
Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases
Soto, C., & Pritzkow, S. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0235-9 · Cited by 1,180 · see citing works
Fibril structure of amyloid-β(1–42) by cryo–electron microscopy
Gremer, L., Schölzel, D., Schenk, C., Reinartz, E., Labahn, J., Ravelli, R. B. G., Tusche, M., López‐Iglesias, C., Hoyer, W., Heise, H., et al. (2017) · Science · doi:10.1126/science.aao2825 · Cited by 1,031 · see citing works
A new era for understanding amyloid structures and disease
Iadanza, M. G., Jackson, M. P., Hewitt, E. W., Ranson, N. A., & Radford, S. E. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0060-8 · Cited by 969 · see citing works
Structure-based classification of tauopathies
Shi, Y., Zhang, W., Yang, Y., Murzin, A. G., Falcon, B., Kotecha, A., van Beers, M., Tarutani, A., Kametani, F., Garringer, H. J., et al. (2021) · Nature · doi:10.1038/s41586-021-03911-7 · Cited by 878 · see citing works
Self-citationStructures of filaments from Pick’s disease reveal a novel tau protein fold
Falcon, B., Zhang, W., Murzin, A. G., Murshudov, G. N., Garringer, H. J., Vidal, R., Crowther, R. A., Ghetti, B. F., Scheres, S. H. W., & Goedert, M. (2018) · Nature · doi:10.1038/s41586-018-0454-y · Cited by 837 · see citing works
Self-citationReconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease
Kametani, F., & Hasegawa, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00025 · Cited by 836 · see citing works
Structures of α-synuclein filaments from multiple system atrophy
Schweighauser, M., Shi, Y., Tarutani, A., Kametani, F., Murzin, A. G., Ghetti, B. F., Matsubara, T., Tomita, T., Ando, T., Hasegawa, K., et al. (2020) · Nature · doi:10.1038/s41586-020-2317-6 · Cited by 776 · see citing works
“This finding is also reminiscent of similar results for tau filaments (4-9), even though marked differences exist between tau and α-synuclein.”
BackgroundResultInfluentialSelf-citationStress granules and neurodegeneration
Wolozin, B. L., & Ivanov, P. V. (2019) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0222-5 · Cited by 782 · see citing works
Tau PTM Profiles Identify Patient Heterogeneity and Stages of Alzheimer’s Disease
Wesseling, H., Mair, W., Kumar, M., Schlaffner, C. N., Tang, S., Beerepoot, P., Fatou, B., Guise, A. J., Cheng, L., Takeda, S., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.029 · Cited by 688 · see citing works
“Sixteen of 17 identified ubiquitination sites are in the microtubule binding domain (MBD), which forms the core of the filament (Crowther et al., 1989; Falcon et al., 2018; Fitzpatrick et al., 2017).”
BackgroundNovel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules
Falcon, B., Zivanov, J., Zhang, W., Murzin, A. G., Garringer, H. J., Vidal, R., Crowther, R. A., Newell, K. L., Ghetti, B. F., Goedert, M., et al. (2019) · Nature · doi:10.1038/s41586-019-1026-5 · Cited by 703 · see citing works
Self-citationNguyen, P. H., Ramamoorthy, A., Sahoo, B. R., Zheng, J., Faller, P., Straub, J. E., Domı́nguez, L., Shea, J., Dokholyan, N. V., Simone, A. D., et al. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01122 · Cited by 676 · see citing works
the Dominantly Inherited Alzheimer Network, Barthélemy, N. R., Li, Y., Joseph-Mathurin, N., Gordon, B. A., Hassenstab, J., Benzinger, T. L. S., Buckles, V., Fagan, A. M., Perrin, R. J., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0781-z · Cited by 651 · see citing works
Protein transmission in neurodegenerative disease
Peng, C., Trojanowski, J. Q., & Lee, V. M.-Y. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0333-7 · Cited by 625 · see citing works
Tau PET imaging in neurodegenerative tauopathies—still a challenge
Leuzy, A., Chiotis, K., Lemoine, L., Gillberg, P.-G., Almkvist, O., Rodriguez-Vieitez, E., & Nordberg, A. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0342-8 · Cited by 628 · see citing works
Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel
Li, B., Ge, P., Murray, K. A., Sheth, P., Zhang, M., Nair, G., Sawaya, M. R., Shin, W. S., Boyer, D. R., Ye, S., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05971-2 · Cited by 623 · see citing works
Peptide-Based Vaccines: Current Progress and Future Challenges
Malonis, R. J., Lai, J. R., & Vergnolle, O. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00472 · Cited by 602 · see citing works
“96 The core Tau filament is composed of residues 306−378 of Tau, forming a combined cross-β/β-helix structure of two protofilaments (paired helical and straight filaments, Figure 8 ).”
BackgroundCryo-EM structure of alpha-synuclein fibrils
Guerrero-Ferreira, R., Taylor, N. M. I., Mona, D., Ringler, P., Lauer, M. E., Riek, R., Britschgi, M., & Stahlberg, H. (2018) · eLife · doi:10.7554/elife.36402 · Cited by 600 · see citing works
“However, similar structural characteristics have been previously observed for pathological tau filaments obtained from Alzheimer’s disease brains where (i): lysine and tyrosine residues play a similarly stabilizing role in the interface region of two protofilaments of the straight filaments (SF), and (ii): the area in…”
BackgroundMethodInfluentialSelective vulnerability in neurodegenerative diseases
Fu, H., Hardy, J., & Duff, K. E. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0221-2 · Cited by 585 · see citing works
Tau Kinetics in Neurons and the Human Central Nervous System
Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.015 · Cited by 586 · see citing works
Half a century of amyloids: past, present and future
Ke, P. C., Zhou, R., Serpell, L. C., Riek, R., Knowles, T. P. J., Lashuel, H. A., Gazit, E., Hamley, I. W., Davis, T. P., Fändrich, M., et al. (2020) · Chemical Society Reviews · doi:10.1039/c9cs00199a · Cited by 567 · see citing works
Cryo-EM structures of amyloid-β 42 filaments from human brains
Yang, Y., Arseni, D., Zhang, W., Huang, M., Lövestam, S., Schweighauser, M., Kotecha, A., Murzin, A. G., Peak-Chew, S. Y., Macdonald, J., et al. (2022) · Science · doi:10.1126/science.abm7285 · Cited by 546 · see citing works
Self-citationNovel tau filament fold in corticobasal degeneration
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. (2020) · Nature · doi:10.1038/s41586-020-2043-0 · Cited by 546 · see citing works
Self-citationLRP1 is a master regulator of tau uptake and spread
Rauch, J. N., Luna, G., Guzman, E., Audouard, M., Challis, C., Sibih, Y. E., Leshuk, C., Hernandez, I., Wegmann, S., Hyman, B. T., et al. (2020) · Nature · doi:10.1038/s41586-020-2156-5 · Cited by 541 · see citing works
Phase separation and neurodegenerative diseases: a disturbance in the force
Zbinden, A., Pérez-Berlanga, M., De Rossi, P., & Polymenidou, M. (2020) · Developmental Cell · doi:10.1016/j.devcel.2020.09.014 · Cited by 500 · see citing works
α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis
Mehra, S., Sahay, S., & Maji, S. K. (2019) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2019.03.001 · Cited by 507 · see citing works
Zhang, W., Falcon, B., Murzin, A. G., Fan, J., Crowther, R. A., Goedert, M., & Scheres, S. H. W. (2019) · eLife · doi:10.7554/elife.43584 · Cited by 500 · see citing works
“We previously hypothesized that neutralising, negative charges could also be provided by residues in the fuzzy coat (Fitzpatrick et al., 2017).”
BackgroundMethodInfluentialSelf-citationThe expanding amyloid family: Structure, stability, function, and pathogenesis
Sawaya, M. R., Hughes, M. P., Rodriguez, J. A., Riek, R., & Eisenberg, D. S. (2021) · Cell · doi:10.1016/j.cell.2021.08.013 · Cited by 475 · see citing works
Converging pathways in neurodegeneration, from genetics to mechanisms
Gan, L., Cookson, M. R., Petrucelli, L., & Spada, A. R. L. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0237-7 · Cited by 475 · see citing works
Propagation and spread of pathogenic protein assemblies in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0238-6 · Cited by 450 · see citing works
Secondary nucleation in amyloid formation
Törnquist, M., Michaels, T. C. T., Sanagavarapu, K., Yang, X., Meisl, G., Cohen, S. I. A., Knowles, T. P. J., & Linse, S. S. (2018) · Chemical Communications · doi:10.1039/c8cc02204f · Cited by 459 · see citing works
Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Dujardin, S., Commins, C., Lathuiliere, A., Beerepoot, P., Fernandes, A. R., Kamath, T. V., De Los Santos, M. B., Klickstein, N., Corjuc, D. L., Corjuc, B. T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0938-9 · Cited by 438 · see citing works
Cryo-EM in drug discovery: achievements, limitations and prospects
Renaud, J., Chari, A., Ciferri, C., Liu, W.-T., Rémigy, H., Stark, H., & Wiesmann, C. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.77 · Cited by 459 · see citing works
Near-atomic model of microtubule-tau interactions
Kellogg, E. H., Hejab, N. M. A., Poepsel, S., Downing, K. H., DiMaio, F., & Nogales, E. (2018) · Science · doi:10.1126/science.aat1780 · Cited by 416 · see citing works
Amyloid fibril structure of α-synuclein determined by cryo-electron microscopy
Li, Y., Zhao, C., Luo, F., Liu, Z., Gui, X., Luo, Z., Zhang, X., Li, D., Liu, C., & Li, X. (2018) · Cell Research · doi:10.1038/s41422-018-0075-x · Cited by 432 · see citing works
Alzheimer’s disease: insights into pathology, molecular mechanisms, and therapy
Zheng, Q., & Wang, X. (2024) · Protein & Cell · doi:10.1093/procel/pwae026 · Cited by 454 · see citing works
Alpha-synuclein structure and Parkinson’s disease – lessons and emerging principles
Meade, R. M., Fairlie, D. P., & Mason, J. M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0329-1 · Cited by 430 · see citing works
MAPT mutations, tauopathy, and mechanisms of neurodegeneration
Strang, K. H., Golde, T. E., & Giasson, B. I. (2019) · Laboratory Investigation · doi:10.1038/s41374-019-0197-x · Cited by 424 · see citing works
Congo Red and amyloids: history and relationship
Yakupova, E. I., Bobyleva, L. G., Vikhlyantsev, I. M., & Bobylev, A. G. (2018) · Bioscience Reports · doi:10.1042/bsr20181415 · Cited by 408 · see citing works
Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains
Arakhamia, T., Lee, C. E., Carlomagno, Y., Kumar, M., Duong, D. M., Wesseling, H., Kundinger, S. R., Wang, K., Williams, D., Deture, M. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.01.027 · Cited by 400 · see citing works
Self-citationWhat is the evidence that tau pathology spreads through prion-like propagation?
Mudher, A., Colin, M., Dujardin, S., Medina, M., Dewachter, I., Alavi Naini, S. M., Mandelkow, E.-M., Mandelkow, E., Buée, L., Goedert, M., et al. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0488-7 · Cited by 384 · see citing works
Self-citationRodent models for Alzheimer disease
Götz, J., Bodea, L., & Goedert, M. (2018) · Nature reviews. Neuroscience · doi:10.1038/s41583-018-0054-8 · Cited by 397 · see citing works
Self-citationEmerging diagnostics and therapeutics for Alzheimer disease
Self, W. K., & Holtzman, D. M. (2023) · Nature Medicine · doi:10.1038/s41591-023-02505-2 · Cited by 381 · see citing works
Amyloid-β and tau complexity — towards improved biomarkers and targeted therapies
Polanco, J. C., Li, C., Bodea, L., Martínez‐Mármol, R., Meunier, F. A., & Götz, J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.162 · Cited by 374 · see citing works
The complexity of tau in Alzheimer’s disease
Naseri, N. N., Wang, H., Guo, J. D., Sharma, M., & Luo, W. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.04.022 · Cited by 374 · see citing works
Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold
Falcon, B., Zhang, W., Schweighauser, M., Murzin, A. G., Vidal, R., Garringer, H. J., Ghetti, B., Scheres, S. H. W., & Goedert, M. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1914-z · Cited by 362 · see citing works
“We used antibodies specific for R1 (BR136), R2 (Anti-4R), R3 (BR135) and R4 (TauC4) of tau, all of which label tau bands in Western blots of dissociated filaments (19,20) (Figure 3).”
BackgroundMethodResultInfluentialSelf-citationPhosphorylated tau interactome in the human Alzheimer's disease brain
Drummond, E., Pires, G., MacMurray, C., Askenazi, M., Nayak, S., Bourdon, M., Safar, J., Ueberheide, B., & Wisniewski, T. (2020) · Brain · doi:10.1093/brain/awaa223 · Cited by 357 · see citing works
Alquezar, C., Arya, S., & Kao, A. W. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2020.595532 · Cited by 367 · see citing works
“Interestingly, the core of tau filaments isolated from tauopathy patients contains multiple lysine residues that are susceptible to acetylation (280, 281, 283).”
BackgroundAmyloid Polymorphism in the Protein Folding and Aggregation Energy Landscape
Adamčík, J., & Mezzenga, R. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201713416 · Cited by 345 · see citing works
Multicomponent peptide assemblies
Raymond, D. M., & Nilsson, B. L. (2018) · Chemical Society Reviews · doi:10.1039/c8cs00115d · Cited by 346 · see citing works
Neuropathology and molecular diagnosis of Synucleinopathies
Koga, S., Sekiya, H., Kondru, N. C., Ross, O. A., & Dickson, D. W. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00501-z · Cited by 338 · see citing works
Guerrero-Ferreira, R., Taylor, N. M. I., Arteni, A., Kumari, P., Mona, D., Ringler, P., Britschgi, M., Lauer, M. E., Makky, A., Verasdonck, J., et al. (2019) · eLife · doi:10.7554/elife.48907 · Cited by 338 · see citing works
“Therefore, a-Syn fibrils exhibit assembly polymorphism as defined by Riek (2017) and described in Tau between paired helical filaments (PHFs) and straight filaments (SFs) (Fitzpatrick et al., 2017).”
BackgroundMethodStructure-based inhibitors of tau aggregation
Seidler, P. M., Boyer, D. R., Rodríguez, J. A., Sawaya, M. R., Cascio, D., Murray, K. A., Gonen, T., & Eisenberg, D. S. (2017) · Nature Chemistry · doi:10.1038/nchem.2889 · Cited by 340 · see citing works
“Interpreted this way, our VQIINK structures are consistent with the AD-derived Tau fibril model reported by Fitzpatrick et al (2017).”
Functional AmyloidsPreprint
Otzen, D. E., & Riek, R. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033860 · Cited by 332 · see citing works
“Recent structures of amyloid composed of full-length proteins reveal a much greater structural complexity, involving a combination of multiple cross-β-sheet motifs (Wasmer et al. 2008; Colvin et al. 2016; Riek and Eisenberg 2016; Wälti et al. 2016; Fitzpatrick et al. 2017).”
BackgroundMoloney, C. M., Lowe, V. J., & Murray, M. E. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12321 · Cited by 337 · see citing works
Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility
Karikari, T. K., Ashton, N. J., Brinkmalm, G., Brum, W. S., Benedet, A. L., Montoliu‐Gaya, L., Lantero‐Rodriguez, J., Pascoal, T. A., Suárez‐Calvet, M., Rosa‐Neto, P., et al. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00665-2 · Cited by 327 · see citing works
Propagation of Protein Aggregation in Neurodegenerative Diseases
Vaquer‐Alicea, J., & Diamond, M. I. (2019) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-045049 · Cited by 308 · see citing works
Lövestam, S., Koh, F. A., van Knippenberg, B., Kotecha, A., Murzin, A. G., Goedert, M., & Scheres, S. H. W. (2022) · eLife · doi:10.7554/elife.76494 · Cited by 306 · see citing works
“…determine the atomic structures of the cores of tau filaments extracted from the brains of individuals with a number of neurodegenerative diseases (Fitzpatrick et al., 2017; Falcon, Zhang, Murzin, et al., 2018; Falcon et al., 2019, 2019; Arakhamia et al., 2020; Zhang et al., 2020; Shi et al.,…”
BackgroundSelf-citationMechanisms of secretion and spreading of pathological tau protein
Brunello, C. A., Merezhko, M., Uronen, R.-L., & Huttunen, H. J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03349-1 · Cited by 304 · see citing works
van Oostveen, W. M., & de Lange, E. C. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042110 · Cited by 297 · see citing works
α-Synuclein pathology in Parkinson’s disease and related α-synucleinopathies
Henderson, M. X., Trojanowski, J. Q., & Lee, V. M. ‐. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134316 · Cited by 291 · see citing works
“The recent publication of tau fibril structures from AD [97] and Pick’s disease [98] brains using cryo-EM suggests that this technique has the ability to solve human biosample-derived amyloid structures.”
Molecular pathology of neurodegenerative diseases by cryo-EM of amyloids
Scheres, S. H. W., Falcon, B., & Goedert, M. (2023) · Nature · doi:10.1038/s41586-023-06437-2 · Cited by 293 · see citing works
Self-citationA walk through tau therapeutic strategies
Jadhav, S., Ávila, J., Schöll, M., Kovács, G. G., Kövari, E., Škrabana, R., Evans, L., Kontseková, E., Malawska, B., de Silva, R., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0664-z · Cited by 286 · see citing works
Amyloid structure determination in RELION -3.1
Scheres, S. H. W. (2020) · Acta Crystallographica Section D Structural Biology · doi:10.1107/s2059798319016577 · Cited by 273 · see citing works
Self-citationCryo-EM structures of tau filaments
Scheres, S. H. W., Zhang, W., Falcon, B., & Goedert, M. (2020) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2020.05.011 · Cited by 266 · see citing works
Self-citationThe Hsp70–Hsp90 Chaperone Cascade in Protein Folding
Luengo, T. M., Mayer, M. P., & Rüdiger, S. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.10.004 · Cited by 276 · see citing works
Alzheimer’s disease brain-derived extracellular vesicles spread tau pathology in interneurons
Ruan, Z., Pathak, D., Venkatesan Kalavai, S., Yoshii-Kitahara, A., Muraoka, S., Bhatt, N., Takamatsu-Yukawa, K., Hu, J., Wang, Y., Hersh, S., et al. (2021) · Brain · doi:10.1093/brain/awaa376 · Cited by 283 · see citing works
“A growing body of evidence suggests that misfolded tau tends to be truncated and frequently consists of different conformers or structural polymorphisms, dependent on the stages and disease of tauopathy (Fitzpatrick et al., 2017; Falcon et al., 2018, 2019; Sigurdsson, 2018; Zhang et al., 2020).”
BackgroundMolecular Pathogenesis of the Tauopathies
Götz, J., Halliday, G., & Nisbet, R. M. (2019) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012936 · Cited by 276 · see citing works
Hyperphosphorylation of Tau Associates With Changes in Its Function Beyond Microtubule Stability
Alonso, A. D., Cohen, L. S., Corbo, C., Morozova, V., ElIdrissi, A., Phillips, G., & Kleiman, F. E. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00338 · Cited by 278 · see citing works
“As an IDP, the secondary structure of tau is not defined, however, tau structural information is very important in the formation of PHF/SF in AD brains (Fitzpatrick et al., 2017).”
BackgroundTagai, K., Ono, M., Kubota, M., Kitamura, S., Takahata, K., Seki, C., Takado, Y., Shinotoh, H., Sano, Y., Yamamoto, Y., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.042 · Cited by 269 · see citing works
Kell, D. B., Laubscher, G. J., & Pretorius, E. (2022) · Biochemical Journal · doi:10.1042/bcj20220016 · Cited by 278 · see citing works
CSF MTBR-tau243 is a specific biomarker of tau tangle pathology in Alzheimer’s disease
Horie, K., Salvadó, G., Barthélemy, N. R., Janelidze, S., Li, Y., He, Y., Saef, B., Chen, C. D., Jiang, H., Strandberg, O., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02443-z · Cited by 249 · see citing works
Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation
Guenther, E. L., Cao, Q., Trinh, H., Lu, J., Sawaya, M. R., Cascio, D., Boyer, D. R., Rodríguez, J. A., Hughes, M. P., & Eisenberg, D. S. (2018) · Nature Structural & Molecular Biology · doi:10.1038/s41594-018-0064-2 · Cited by 247 · see citing works
Mechanisms and pathology of protein misfolding and aggregation
Louros, N. N., Schymkowitz, J., & Rousseau, F. (2023) · Nature reviews. Molecular cell biology · doi:10.1038/s41580-023-00647-2 · Cited by 221 · see citing works
“2), whereas tau forms ultrastructural polymorphs that are classified between different tauopathies and share several different protofilament folds 145–147 . αS forms distinct fibrils in multiple system atrophy (MSA) and Parkinson disease 148,149 .”
BackgroundCryo-EM structures of four polymorphic TDP-43 amyloid cores
Cao, Q., Boyer, D. R., Sawaya, M. R., Ge, P., & Eisenberg, D. S. (2019) · Nature Structural & Molecular Biology · doi:10.1038/s41594-019-0248-4 · Cited by 253 · see citing works
Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy
Cope, T., Rittman, T., Borchert, R. J., Jones, P. S., Vatansever, D., Allinson, K. S. J., Passamonti, L., Rodríguez, P. V., Bevan-Jones, W. R., O'Brien, J. T., et al. (2017) · Brain · doi:10.1093/brain/awx347 · Cited by 240 · see citing works
Inert and seed-competent tau monomers suggest structural origins of aggregation
Mirbaha, H., Chen, D., Morazova, O. A., Ruff, K. M., Sharma, A. M., Liu, X., Goodarzi, M., Pappu, R. V., Colby, D. W., Mirzaei, H., et al. (2018) · eLife · doi:10.7554/elife.36584 · Cited by 234 · see citing works
Schöll, M., Maaß, A., Mattsson, N., Ashton, N. J., Blennow, K., Zetterberg, H., & Jagust, W. J. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.12.001 · Cited by 227 · see citing works
Kroth, H., Oden, F., Molette, J., Schieferstein, H., Capotosti, F., Mueller, A., Berndt, M., Schmitt-Willich, H., Darmency, V., Gabellieri, E., et al. (2019) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-019-04397-2 · Cited by 193 · see citing works
Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts
Strohäker, T., Jung, B. C., Liou, S.-H., Fernández, C. O., Riedel, D., Becker, S., Halliday, G. M., Bennati, M., Kim, W. S., Lee, S., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13564-w · Cited by 224 · see citing works
Cellular and pathological heterogeneity of primary tauopathies
Chung, D. C., Roemer, S. F., Petrucelli, L., & Dickson, D. W. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00476-x · Cited by 219 · see citing works
Enzymatic Noncovalent Synthesis
He, H., Tan, W., Guo, J., Yi, M., Shy, A. N., & Xu, B. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.0c00306 · Cited by 222 · see citing works
Amyloid-type Protein Aggregation and Prion-like Properties of Amyloids
Willbold, D., Strodel, B., Schroeder, G. F., Hoyer, W., & Heise, H. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00196 · Cited by 222 · see citing works
Tau aggregates are RNA-protein assemblies that mislocalize multiple nuclear speckle components
Lester, E., Ooi, F. K., Bakkar, N., Ayers, J. I., Woerman, A. L., Wheeler, J., Bowser, R. P., Carlson, G. A., Prusiner, S. B., & Parker, R. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.026 · Cited by 212 · see citing works
Xia, Y., Prokop, S., & Giasson, B. I. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00460-5 · Cited by 218 · see citing works
Disease-specific tau filaments assemble via polymorphic intermediates
Lövestam, S., Li, D., Wagstaff, J. L., Kotecha, A., Kimanius, D., McLaughlin, S. H., Murzin, A. G., Freund, S. M. V., Goedert, M., & Scheres, S. H. W. (2023) · Nature · doi:10.1038/s41586-023-06788-w · Cited by 202 · see citing works
“The tau(297–391) construct, upon shaking in phosphate buffer with magnesium chloride, forms PHFs with ordered cores that are identical to those from human brains 3,8 .”
BackgroundSelf-citationZhao, K., Lim, Y., Liu, Z., Long, H., Sun, Y., Hu, J., Zhao, C., Tao, Y., Zhang, X., Li, D., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922741117 · Cited by 198 · see citing works
Tapia‐Rojas, C., Cabezas-Opazo, F., Deaton, C. A., Vergara, E. H., Johnson, G. V. W., & Quintanilla, R. A. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.005 · Cited by 195 · see citing works
Tau local structure shields an amyloid-forming motif and controls aggregation propensity
Chen, D., Drombosky, K. W., Hou, Z., Sari, L., Kashmer, O. M., Ryder, B. D., Perez, V. A., Woodard, D. R., Lin, M. M., Diamond, M. I., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-10355-1 · Cited by 196 · see citing works
“To test whether isomerization of P301 could influence spontaneous amyloid formation, we constructed a series of R2R3 peptide fragments with proline analogs that preferentially populate either: (1) a cis rotamer (2S,4S)fluoroproline; (2) a trans rotamer (2S,4R)-fluoroproline; or (3) an analog that easily interconverts…”
BackgroundPaonessa, F., Evans, L., Solanki, R., Larrieu, D., Wray, S., Hardy, J., Jackson, S. P., & Livesey, F. J. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.085 · Cited by 189 · see citing works
“Protein aggregation is widely considered as inherently pathogenic in neurodegeneration (Fitzpatrick et al., 2017; Hernández-Vega et al., 2017), altering many cellular functions, most notably autophagy and proteostasis (Bence et al.”
BackgroundSchmidt, M., Wiese, S., Adak, V., Engler, J., Agarwal, S., Fritz, G., Westermark, P., Zacharias, M., & Fändrich, M. (2019) · Nature Communications · doi:10.1038/s41467-019-13038-z · Cited by 194 · see citing works
Age-dependent formation of TMEM106B amyloid filaments in human brains
Schweighauser, M., Arseni, D., Bacioglu, M., Huang, M., Lövestam, S., Shi, Y., Yang, Y., Zhang, W., Kotecha, A., Garringer, H. J., et al. (2022) · Nature · doi:10.1038/s41586-022-04650-z · Cited by 194 · see citing works
Self-citationMueller, A., Bullich, S., Barret, O., Madonia, J., Berndt, M., Papin, C., Perrotin, A., Koglin, N., Kroth, H., Pfeifer, A., et al. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.119.236224 · Cited by 191 · see citing works
“The same protein sequences can also lead to disease-specific folds of tau filaments, as in AD and chronic traumatic encephalopathy, in which all 6 tau isoforms are present (8,9).”
BackgroundAcetylation Disfavors Tau Phase Separation
Ferreon, J. C., Jain, A., Choi, K.-J., Tsoi, P. S., MacKenzie, K. R., Jung, S. Y., & Ferreon, A. C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051360 · Cited by 183 · see citing works
From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy
Colin, M., Dujardin, S., Schraen-Maschke, S., Meno-Tetang, G., Duyckaerts, C., Courade, J.-P., & Buée, L. (2020) · Acta Neuropathologica · doi:10.1007/s00401-019-02087-9 · Cited by 187 · see citing works
Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue
Ghosh, U., Thurber, K. R., Yau, W., & Tycko, R. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023089118 · Cited by 190 · see citing works
Amyloid structures: much more than just a cross-β fold
Gallardo, R. U., Ranson, N. A., & Radford, S. E. (2019) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2019.09.001 · Cited by 189 · see citing works
Lövestam, S., Schweighauser, M., Matsubara, T., Murayama, S., Tomita, T., Ando, T., Hasegawa, K., Yoshida, M., Tarutani, A., Hasegawa, M., et al. (2021) · FEBS Open Bio · doi:10.1002/2211-5463.13110 · Cited by 183 · see citing works
Self-citation
- 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 · 2014: 1 · 2013: 1
- 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
- Health Sciences › Medicine › Physiology › 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 ›
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