Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Novel tau filament fold in corticobasal degeneration


Corticobasal degeneration (CBD) is a neurodegenerative tauopathy—a class of disorders in which the tau protein forms insoluble inclusions in the brain—that is characterized by motor and cognitive disturbances1,2,3. The H1 haplotype of MAPT (the tau gene) is present in cases of CBD at a higher frequency than in controls4,5, and genome-wide association studies have identified additional risk factors6. By histology, astrocytic plaques are diagnostic of CBD7,8; by SDS–PAGE, so too are detergent-insoluble, 37 kDa fragments of tau9. Like progressive supranuclear palsy, globular glial tauopathy and argyrophilic grain disease10, CBD is characterized by abundant filamentous tau inclusions that are made of isoforms with four microtubule-binding repeats11,12,13,14,15. This distinguishes such ‘4R’ tauopathies from Pick’s disease (the filaments of which are made of three-repeat (3R) tau isoforms) and from Alzheimer’s disease and chronic traumatic encephalopathy (CTE) (in which both 3R and 4R isoforms are found in the filaments)16. Here we use cryo-electron microscopy to analyse the structures of tau filaments extracted from the brains of three individuals with CBD. These filaments were identical between cases, but distinct from those seen in Alzheimer’s disease, Pick’s disease and CTE17,18,19. The core of a CBD filament comprises residues lysine 274 to glutamate 380 of tau, spanning the last residue of the R1 repeat, the whole of the R2, R3 and R4 repeats, and 12 amino acids after R4. The core adopts a previously unseen four-layered fold, which encloses a large nonproteinaceous density. This density is surrounded by the side chains of lysine residues 290 and 294 from R2 and lysine 370 from the sequence after R4.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Filamentous tau pathology of CBD.
Fig. 2: Cryo-EM maps of CBD type I and type II tau filaments, and atomic model of type II filaments.
Fig. 3: Structures of tau filament cores from human brain.

Data availability

Cryo-EM maps for CBD case 1 have been deposited in the Electron Microscopy Data Bank (EMDB; under accession numbers EMD-10512 for CBD type I and EMD-10514 for CBD type II filaments. The refined atomic models for CBD type I and type II tau filaments have been deposited in the Protein Data Bank (PDB; under accession numbers 6TJO and 6TJX, respectively. Whole-exome and whole-genome sequencing data and repeat-primed polymerase chain reaction C9orf72 hexanucleotide repeat expansion data have been deposited in the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS;, under accession number NG00098. Any other relevant data are available from the corresponding authors upon reasonable request.


  1. 1.

    Lhermitte, J., Lévy, G. & Kyriaco, N. Les perturbations de la représentation spatiale chez les apraxiques. Rev. Neurol. (Paris) 2, 586–600 (1925).

    Google Scholar 

  2. 2.

    Rebeiz, J. J., Kolodny, E. H. & Richardson, E. P. Jr. Corticodentatonigral degeneration with neuronal achromasia. Arch. Neurol. 18, 20–33 (1968).

    CAS  PubMed  Google Scholar 

  3. 3.

    Gibb, W. R. G., Luthert, P. J. & Marsden, C. D. Corticobasal degeneration. Brain 112, 1171–1192 (1989).

    PubMed  Google Scholar 

  4. 4.

    Di Maria, E. et al. Corticobasal degeneration shares a common genetic background with progressive supranuclear palsy. Ann. Neurol. 47, 374–377 (2000).

    PubMed  Google Scholar 

  5. 5.

    Houlden, H. et al. Corticobasal degeneration and progressive supranuclear palsy share a common tau haplotype. Neurology 56, 1702–1706 (2001).

    CAS  PubMed  Google Scholar 

  6. 6.

    Kouri, N. et al. Genome-wide association study of corticobasal degeneration identifies risk variants shared with progressive supranuclear palsy. Nat. Commun. 6, 7247 (2015).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Feany, M. B. & Dickson, D. W. Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am. J. Pathol. 146, 1388–1396 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Komori, T. et al. Astrocytic plaques and tufts of abnormal fibers do not coexist in corticobasal degeneration and progressive supranuclear palsy. Acta Neuropathol. 96, 401–408 (1998).

    CAS  PubMed  Google Scholar 

  9. 9.

    Arai, T. et al. Identification of amino-terminally cleaved tau fragments that distinguish progressive supranuclear palsy from corticobasal degeneration. Ann. Neurol. 55, 72–79 (2004).

    CAS  PubMed  Google Scholar 

  10. 10.

    Rösler, T. W. et al. Four-repeat tauopathies. Prog. Neurobiol. 180, 101644 (2019).

    PubMed  Google Scholar 

  11. 11.

    Paulus, W. & Selim, M. Corticonigral degeneration with neuronal achromasia and basal neurofibrillary tangles. Acta Neuropathol. 81, 89–94 (1990).

    CAS  PubMed  Google Scholar 

  12. 12.

    Wakabayashi, K. et al. Corticobasal degeneration: etiopathological significance of the cytoskeletal alterations. Acta Neuropathol. 87, 545–553 (1994).

    CAS  PubMed  Google Scholar 

  13. 13.

    Ksiezak-Reding, H. et al. Ultrastructure and biochemical composition of paired helical filaments in corticobasal degeneration. Am. J. Pathol. 145, 1496–1508 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Arima, K. et al. Corticonigral degeneration with neuronal achromasia presenting with primary progressive aphasia: ultrastructural and immunocytochemical studies. J. Neurol. Sci. 127, 186–197 (1994).

    CAS  PubMed  Google Scholar 

  15. 15.

    Sergeant, N., Wattez, A. & Delacourte, A. Neurofibrillary degeneration in progressive supranuclear palsy and corticobasal degeneration: tau pathologies with exclusively “exon 10” isoforms. J. Neurochem. 72, 1243–1249 (1999).

    CAS  PubMed  Google Scholar 

  16. 16.

    Goedert, M., Eisenberg, D. S. & Crowther, R. A. Propagation of tau aggregates and neurodegeneration. Annu. Rev. Neurosci. 40, 189–210 (2017).

    CAS  PubMed  Google Scholar 

  17. 17.

    Fitzpatrick, A. W. P. et al. Cryo-EM structures of tau filaments from Alzheimer’s disease. Nature 547, 185–190 (2017).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Falcon, B. et al. Structures of filaments from Pick’s disease reveal a novel tau protein fold. Nature 561, 137–140 (2018).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Falcon, B. et al. Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. Nature 568, 420–423 (2019).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Taniguchi-Watanabe, S. et al. Biochemical classification of tauopathies by immunoblot, protein sequence and mass spectrometric analyses of sarkosyl-insoluble and trypsin-resistant tau. Acta Neuropathol. 131, 267–280 (2016).

    CAS  PubMed  Google Scholar 

  21. 21.

    Ksiezak-Reding, H. et al. Ultrastructural instability of paired helical filaments from corticobasal degeneration as examined by scanning transmission electron microscopy. Am. J. Pathol. 149, 639–651 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Robinson, J. L. et al. Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain 141, 2181–2193 (2018).

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Uryu, K. et al. Concomitant TAR-DNA-binding protein 43 pathology is present in Alzheimer disease and corticobasal degeneration but not in other tauopathies. J. Neuropathol. Exp. Neurol. 67, 555–564 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Cali, C. P. et al. C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy. Acta Neuropathol. 138, 795–811 (2019).

    PubMed  Google Scholar 

  25. 25.

    He, S. & Scheres, S. H. W. Helical reconstruction in RELION. J. Struct. Biol. 198, 163–176 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Ling, H. et al. Astrogliopathy predominates the earliest stage of corticobasal degeneration pathology. Brain 139, 3237–3252 (2016).

    PubMed  Google Scholar 

  27. 27.

    Shibuya, K., Yagishita, S., Nakamura, A. & Uchihara, T. Perivascular orientation of astrocytic plaques and tuft-shaped astrocytes. Brain Res. 1404, 50–54 (2011).

    CAS  PubMed  Google Scholar 

  28. 28.

    Goedert, M., Spillantini, M. G., Jakes, R., Rutherford, D. & Crowther, R. A. Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer’s disease. Neuron 3, 519–526 (1989).

    CAS  PubMed  Google Scholar 

  29. 29.

    Clavaguera, F. et al. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc. Natl Acad. Sci. USA 110, 9535–9540 (2013).

    ADS  CAS  PubMed  Google Scholar 

  30. 30.

    Sanders, D. W. et al. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82, 1271–1288 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Narasimhan, S. et al. Pathological tau strains from human brains recapitulate the diversity of tauopathies in nontransgenic mouse brain. J. Neurosci. 37, 11406–11423 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. 32.

    von Bergen, M. et al. Assembly of τ protein into Alzheimer paired helical filaments depends on a local sequence motif (306VQIVYK311) forming β structure. Proc. Natl Acad. Sci. USA 97, 5129–5134 (2000).

    ADS  Google Scholar 

  33. 33.

    von Bergen, M. et al. Mutations of tau protein in frontotemporal dementia promote aggregation of paired helical filaments by enhancing local β-structure. J. Biol. Chem. 276, 48165–48174 (2001).

    Google Scholar 

  34. 34.

    Falcon, B. et al. Conformation determines the seeding potencies of native and recombinant Tau aggregates. J. Biol. Chem. 290, 1049–1065 (2015).

    CAS  PubMed  Google Scholar 

  35. 35.

    Macdonald, J. A. et al. Assembly of transgenic human P301S Tau is necessary for neurodegeneration in murine spinal cord. Acta Neuropathol. Commun. 7, 44 (2019).

    PubMed  PubMed Central  Google Scholar 

  36. 36.

    Gustke, N., Trinczek, B., Biernat, J., Mandelkow, E. M. & Mandelkow, E. Domains of tau protein and interactions with microtubules. Biochemistry 33, 9511–9522 (1994).

    CAS  PubMed  Google Scholar 

  37. 37.

    Zhang, W. et al. Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases. eLife 8, e43584 (2019).

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Dan, A. et al. Extensive deamidation at asparagine residue 279 accounts for weak immunoreactivity of tau with RD4 antibody in Alzheimer’s disease brain. Acta Neuropathol. Commun. 1, 54 (2013).

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Kara, E. et al. The MAPT p.A152T variant is a risk factor associated with tauopathies with atypical clinical and neuropathological features. Neurobiol. Aging 33, 2231.e7–2231.e14 (2012).

    CAS  Google Scholar 

  40. 40.

    Coppola, G. et al. Evidence for a role of the rare p.A152T variant in MAPT in increasing the risk for FTD-spectrum and Alzheimer’s diseases. Hum. Mol. Genet. 21, 3500–3512 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Conrad, C. et al. Differences in a dinucleotide repeat polymorphism in the tau gene between Caucasian and Japanese populations: implication for progressive supranuclear palsy. Neurosci. Lett. 250, 135–137 (1998).

    CAS  PubMed  Google Scholar 

  42. 42.

    Evans, W. et al. The tau H2 haplotype is almost exclusively Caucasian in origin. Neurosci. Lett. 369, 183–185 (2004).

    CAS  PubMed  Google Scholar 

  43. 43.

    Farlow, J. L. et al. Whole-exome sequencing in familial Parkinson disease. JAMA Neurol. 73, 68–75 (2016).

    PubMed  PubMed Central  Google Scholar 

  44. 44.

    Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Goedert, M., Spillantini, M. G., Cairns, N. J. & Crowther, R. A. Tau proteins of Alzheimer paired helical filaments: abnormal phosphorylation of all six brain isoforms. Neuron 8, 159–168 (1992).

    CAS  PubMed  Google Scholar 

  46. 46.

    de Silva, R. et al. Pathological inclusion bodies in tauopathies contain distinct complements of tau with three or four microtubule-binding repeat domains as demonstrated by new specific monoclonal antibodies. Neuropathol. Appl. Neurobiol. 29, 288–302 (2003).

    PubMed  Google Scholar 

  47. 47.

    Mercken, M. et al. Monoclonal antibodies with selective specificity for Alzheimer Tau are directed against phosphatase-sensitive epitopes. Acta Neuropathol. 84, 265–272 (1992).

    CAS  PubMed  Google Scholar 

  48. 48.

    Hasegawa, M. et al. Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann. Neurol. 64, 60–70 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Inukai, Y. et al. Abnormal phosphorylation of Ser409/410 of TDP-43 in FTLD-U and ALS. FEBS Lett. 582, 2899–2904 (2008).

    CAS  PubMed  Google Scholar 

  50. 50.

    Ebashi, M. et al. Detection of AD-specific four repeat tau with deamidated asparagine residue 279-specific fraction purified from 4R tau polyclonal antibody. Acta Neuropathol. 138, 163–166 (2019).

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    Spina, S. et al. The tauopathy associated with mutation +3 in intron 10 of Tau: characterization of the MSTD family. Brain 131, 72–89 (2008).

    PubMed  Google Scholar 

  52. 52.

    Gallyas, F. Silver staining of Alzheimer’s neurofibrillary changes by means of physical development. Acta Morphol. Acad. Sci. Hung. 19, 1–8 (1971).

    CAS  PubMed  Google Scholar 

  53. 53.

    Braak, H., Braak, E., Ohm, T. & Bohl, J. Silver impregnation of Alzheimer’s neurofibrillary changes counterstained for basophilic material and lipofuscin pigment. Stain Technol. 63, 197–200 (1988).

    CAS  PubMed  Google Scholar 

  54. 54.

    Nonaka, T., Watanabe, S. T., Iwatsubo, T. & Hasegawa, M. Seeded aggregation and toxicity of α-synuclein and tau: cellular models of neurodegenerative diseases. J. Biol. Chem. 285, 34885–34898 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. 55.

    Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).

    ADS  CAS  PubMed  PubMed Central  Google Scholar 

  57. 57.

    Scheres, S. H. W. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Scheres, S. H. W. Amyloid structure determination in RELION-3.1. Acta Crystallogr. D 76, 94–101 (2020).

    Google Scholar 

  60. 60.

    Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24–35 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Zivanov, J., Nakane, T. & Scheres, S. H. W. A Bayesian approach to beam-induced motion correction in cryo-EM single-particle analysis. IUCrJ 6, 5–17 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).

    CAS  PubMed  Google Scholar 

  63. 63.

    Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010).

    CAS  PubMed  Google Scholar 

  64. 64.

    Murshudov, G. N., Vagin, A. A. & Dodson, E. J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53, 240–255 (1997).

    CAS  PubMed  Google Scholar 

  65. 65.

    Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references


We thank the patients’ families for donating brain tissues; F. Epperson, R. M. Richardson and U. Kuederli for brain collection and technical support with neuropathology; T. Nakane for help with RELION; G. Murshudov and R. Warshamanage for help with REFMAC; P. Emsley for help with Coot; T. Darling and J. Grimmett for help with high-performance computing; and R. A. Crowther and S. Lovestam for helpful discussions. W.Z. was supported by a foundation that prefers to remain anonymous. M.G. is an Honorary Professor in the Department of Clinical Neurosciences of the University of Cambridge. This work was supported by the UK Medical Research Council (MRC) (grants MC_U105184291 to M.G. and MC_UP_A025_1013 to S.H.W.S.); the European Union (Joint Programme-Neurodegeneration Research REfrAME, to B.F. and M.G., and the EU/EFPIA/Innovative Medicines Initiative [2] Joint Undertaking IMPRiND, project 116060, to M.G.); the Japan Agency for Science and Technology (Crest, grant JPMJCR18H3, to M.H.); the Japan Agency for Medical Research and Development (grants JP18ek0109391 and JP18dm020719 to M.H., and JP19ek0109392 to T.I.); the US National Institutes of Health (grants P30AGO10133 and UO1NS110437 to R.V. and B.G.); and the Department of Pathology and Laboratory Medicine, Indiana University School of Medicine (to R.V. and B.G.). This study was supported by the MRC Laboratory of Molecular Biology (LMB) electron microscopy facility. We acknowledge the Center for Medical Genomics of Indiana University School of Medicine for next-generation DNA sequencing.

Author information




A.T., K.L.N., T.M., S.M., B.G. and M.H. identified patients, performed neuropathology and extracted tau filaments from CBD cases 1 and 2; R.V., H.J.G. and T.I. carried out genetic analyses; W.Z. extracted tau filaments from CBD case 3 and conducted immunolabelling of tau filaments from CBD cases 1–3; W.Z. and B.F. performed cryo-EM; W.Z., Y.S. and S.H.W.S. analysed the cryo-EM data; W.Z. and A.G.M. built the atomic models; A.T. and M.H. carried out seeded aggregation; M.G. and S.H.W.S. supervised the project; all authors contributed to writing the manuscript.

Corresponding authors

Correspondence to Michel Goedert or Sjors H. W. Scheres.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature thanks Jawdat Al-Bassam, Edward Egelman and Markus Zweckstetter for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data figures and tables

Extended Data Fig. 1 Immunolabelling of tau filaments extracted from the frontal cortex of CBD cases 1–3.

Representative immunogold negative-stain electron microscopy images of type I and type II tau filaments extracted from the frontal cortex of CBD cases 1–3. Filaments were labelled with antibodies BR133, BR136 and BR134. Antibodies anti-4R, BR135 and TauC4 did not label filaments, indicating that their epitopes lie within the ordered filament cores. Scale bars, 50 nm.

Extended Data Fig. 2 Immunolabelling of tau filaments extracted from additional brain regions of CBD cases 1–3.

Representative immunogold negative-stain electron microscopy images of type I and type II tau filaments extracted from the putamen of CBD cases 1–3, and from the globus pallidus and thalamus of CBD case 3. Similar to filaments extracted from frontal cortex (Extended Data Fig. 1), tau filaments were labelled with antibodies BR133, BR136 and BR134, but not with antibodies anti-4R, BR135 and TauC4. Scale bars, 50 nm.

Extended Data Fig. 3 Assembled TDP-43 in the frontal cortex of CBD cases 1–3.

Immunoblots were obtained using anti-phosphorylated-TDP-43 antibody. Sarkosyl-insoluble material was prepared as described and all the samples were applied to the same gel. The 43 kDa band (*) corresponds to full-length TDP-43 and the 18–26 kDa bands (**) to C-terminal fragments. The experiment was repeated twice with similar results.

Extended Data Fig. 4 Cryo-EM images and characteristics of tau filaments from the frontal cortex of CBD cases 1–3.

a, Representative cryo-EM images. Total numbers of acquired micrographs are shown in Extended Data Table 1. Scale bars, 20 nm. b, Characteristics of tau filaments. Minimum width, maximum width and crossover distance were measured by hand from the cryo-EM images. Graphs show the mean, standard deviation and individual values from n = 25 independent measurements for each filament type and each CBD case. Statistical analyses of these measurements were performed using a one-way ANOVA, followed by Tukey’s multiple comparisons test; n.s., not significant.

Extended Data Fig. 5 Cryo-EM map and model comparisons.

a, b, Fourier shell correlation curves between two independently refined half-maps (black solid curves), of the final model versus the full map (red solid curves), of a model refined in the first half-map versus the first half-map (green solid curves), and of the same model versus the second half-map (blue dashed curves) for CBD type I (a) and type II (b) filaments. c, d, Local resolution estimates for the CBD type I (c) and type II (d) filament reconstructions. e, f, Side views of the 3D reconstructions of CBD type I (e) and type II (f) filaments. g, h, Sharpened, high-resolution cryo-EM maps of CBD type I (g) and type II (h) tau filaments with their corresponding atomic models overlaid.

Extended Data Fig. 6 CBD tau filament fold.

a, Diagram showing the CBD fold. b, Rendered view of the secondary structure elements in the CBD fold, depicted as three successive rungs. c, As for b, but in a view perpendicular to the helical axis, revealing the changes in height within a single molecule. d, Comparison of the protofilament structures of CBD type I (blue) and type II (pink).

Extended Data Fig. 7 Protofilament interface in CBD type II tau filaments.

Packing between residues 343KLDFKDR349 of the two protofilaments. Interprotofilament hydrogen bonds are in yellow; intraprotofilament hydrogen bonds are in green.

Extended Data Fig. 8 Seeded tau aggregation induced by CBD filaments in SH-SY5Y cells.

a, Immunoblotting of sarkosyl-insoluble (Ppt) and sarkosyl-soluble (Sup) fractions extracted from mock-transfected SH-SY5Y cells and from cells transfected with tau seeds from the frontal cortex of CBD cases 1–3. SH-SY5Y cells transiently expressed either haemagglutinin (HA)-tagged 1N4R or HA-tagged 1N3R human tau. Insoluble tau was detected with anti-HA and anti-pS396 antibodies. Total tau was detected with anti-TauC. Blotting with an anti-α-tubulin antibody served as a loading control. b, Quantification of anti-HA-positive bands. The results are expressed as the mean ± s.e.m. (n = 3).

Extended Data Table 1 Cryo-EM data collection, refinement and validation statistics

Supplementary information

Supplementary Figure 1

This file contains source images for Western blots. (a), Source images for Western blots shown in Fig. 1g. (b), Source images for Western blots shown in Extended_Data_Fig. 3. (c) Source images for Western blots shown in Extended_Data_Figure 8a.

Reporting Summary

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Zhang, W., Tarutani, A., Newell, K.L. et al. Novel tau filament fold in corticobasal degeneration. Nature 580, 283–287 (2020).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing