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Structural characterization of the core of the paired helical filament of Alzheimer disease.
Open accessAbstract
The paired helical filament, the principal constituent of the neurofibrillary tangles characteristic of Alzheimer disease, is shown to consist of two structurally distinct parts. An external fuzzy region can be removed by Pronase treatment to leave a Pronase-resistant morphologically recognizable core. Scanning transmission electron microscopy gives an estimate for the mass per unit length as 79 kDa.nm-1 before Pronase treatment and 65 kDa.nm-1 after treatment. The fuzzy region carries all the epitopes recognized by two different antisera against microtubule-associated protein tau. By contrast, a monoclonal antibody (mAb) we have raised to paired helical filament cores (mAb 423) decorates Pronase-treated filaments much more strongly than it does untreated ones. We have shown in previous papers that the epitope recognized by mAb 423 is carried by a central 9.5-kDa fragment of tau protein, which therefore forms part of the Pronase-resistant core structure. The remainder of the tau protein incorporated into the filaments must contribute part, if not all, of the fuzzy region. The mass per unit length measurements imply that the three-domain structural subunit of the core that we visualized previously by image reconstruction has a molecular mass of approximately equal to 100 kDa.
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Cites
Goedert, M., Wischik, C. M., Crowther, R. A., Walker, J. E., & Klug, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.11.4051 · Cited by 1,134
Self-citation
Cited by
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
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-citationCryo-EM structures of tau filaments from Alzheimer’s disease
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. (2017) · Nature · doi:10.1038/nature23002 · Cited by 2,061
Self-citationAlzheimer’s Disease: The Challenge of the Second Century
Holtzman, D. M., Morris, J. C., & Goate, A. M. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002369 · Cited by 1,424
Goedert, M., Spillantini, M. G., Potier, M. C., Ulrich, J., & Crowther, R. A. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03390.x · Cited by 1,037
Self-citationRoles of tau protein in health and disease
Guo, T., Noble, W., & Hanger, D. P. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1707-9 · Cited by 1,003
Goedert, M., & Jakes, R. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07870.x · Cited by 929
Bramblett, G. T., Goedert, M., Jakes, R., Merrick, S. E., Trojanowski, J. Q., & Lee, V. M. Y. (1993) · Neuron · doi:10.1016/0896-6273(93)90057-x · Cited by 903
Reconsideration 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
Tau and neurodegenerative disease: the story so far
Iqbal, K., Liu, F., & Gong, C.-X. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.225 · Cited by 806
Ambadipudi, S., Biernat, J., Riedel, D., Mandelkow, E., & Zweckstetter, M. (2017) · Nature Communications · doi:10.1038/s41467-017-00480-0 · Cited by 782
Proteopathic tau seeding predicts tauopathy in vivo
Holmes, B. B., Furman, J. L., Mahan, T. E., Yamasaki, T. R., Mirbaha, H., Eades, W. C., Belaygorod, L., Cairns, N. J., Holtzman, D. M., & Diamond, M. I. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411649111 · Cited by 696
Structural Polymorphism of 441-Residue Tau at Single Residue Resolution
Mukrasch, M. D., Bibow, S., Korukottu, J., Jeganathan, S., Biernat, J., Griesinger, C., Mandelkow, E., & Zweckstetter, M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000034 · Cited by 652
Propagation of Tau aggregates and neurodegeneration
Goedert, M., Eisenberg, D. S., & Crowther, R. A. (2017) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-072116-031153 · Cited by 632
Self-citationWu, J. W., Herman, M., Liu, L., Simoes, S., Acker, C. M., Figueroa, H., Steinberg, J. I., Margittai, M., Kayed, R., Zurzolo, C., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.394528 · Cited by 537
Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines.
Wischik, C. M., Edwards, P. C., Lai, R. Y., Roth, M., & Harrington, C. R. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.20.11213 · Cited by 547
Self-citationCaspase-cleavage of tau is an early event in Alzheimer disease tangle pathology
Rissman, R. A., Poon, W. W., Blurton-Jones, M., Oddo, S., Torp, R., Vitek, M. P., LaFerla, F. M., Rohn, T. T., & Cotman, C. W. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200420640 · Cited by 543
Tau stabilizes microtubules by binding at the interface between tubulin heterodimers
Kadavath, H., Hofele, R. V., Biernat, J., Kumar, S., Tepper, K., Urlaub, H., Mandelkow, E., & Zweckstetter, M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1504081112 · Cited by 524
Tau filament formation in transgenic mice expressing P301L tau
Götz, J., Chen, F., Barmettler, R., & Nitsch, R. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m006531200 · Cited by 495
Invited review: Neuropathology of tauopathies: principles and practice
Kovacs, G. G. (2015) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12208 · Cited by 492
An autoradiographic evaluation of AV-1451 Tau PET in dementia
Lowe, V. J., Curran, G., Fang, P., Liesinger, A. M., Josephs, K. A., Parisi, J. E., Kantarci, K., Boeve, B. F., Pandey, M. K., Bruinsma, T., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0315-6 · Cited by 474
Gauthier, S., Feldman, H. H., Schneider, L. S., Wilcock, G. K., Frisoni, G. B., Hardlund, J. H., Moebius, H. J., Bentham, P., Kook, K. A., Wischik, D. J., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31275-2 · Cited by 427
Self-citationGlobal Hairpin Folding of Tau in Solution
Jeganathan, S., von Bergen, M., Brutlach, H., Steinhoff, H.-J., & Mandelkow, E. (2006) · Biochemistry · doi:10.1021/bi0521543 · Cited by 432
What 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
Novak, M., Kabat, J., & Wischik, C. M. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05665.x · Cited by 398
Self-citationTau 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
Jeganathan, S., von Bergen, M., Mandelkow, E.-M., & Mandelkow, E. (2008) · Biochemistry · doi:10.1021/bi800783d · Cited by 286
Acetylated tau, a novel pathological signature in Alzheimer's disease and other tauopathies
Irwin, D. J., Cohen, T. J., Grossman, M., Arnold, S. E., Xie, S. X., Lee, V. M.-Y., & Trojanowski, J. Q. (2012) · Brain · doi:10.1093/brain/aws013 · Cited by 281
Wischik, C. M., Staff, R. T., Wischik, D. J., Bentham, P., Murray, A. D., Storey, J. M. D., Kook, K. A., & Harrington, C. R. (2015) · Journal of Alzheimer's Disease · doi:10.3233/jad-142874 · Cited by 269
Self-citationLuna-Muñoz, J., Chávez-Macías, L., García-Sierra, F., & Mena, R. (2007) · Journal of Alzheimer's Disease · doi:10.3233/jad-2007-12410 · Cited by 233
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220
Early N-Terminal Changes and Caspase-6 Cleavage of Tau in Alzheimer's Disease
Horowitz, P. M., Patterson, K. R., Guillozet-Bongaarts, A. L., Reynolds, M. R., Carroll, C. A., Weintraub, S. T., Bennett, D. A., Cryns, V. L., Berry, R. W., & Binder, L. I. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1988-04.2004 · Cited by 215
Goedert, M., & Spillantini, M. G. (2017) · Molecular Brain · doi:10.1186/s13041-017-0298-7 · Cited by 213
Phosphorylation by cAMP-dependent protein kinase inhibits the degradation of tau by calpain.
Litersky, J. M., & Johnson, G. V. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45982-0 · Cited by 201
The Role of Caspase Cleavage of Tau in Alzheimer Disease Neuropathology
Cotman, C. W., Poon, W. W., Rissman, R. A., & Blurton-Jones, M. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.2.104 · Cited by 199
Ghoshal, N. (2002) · Experimental Neurology · doi:10.1006/exnr.2002.8014 · Cited by 192
Tau Proteins and Neurofibrillary Degeneration
Goedert, M., Spillantini, M. G., & Crowther, R. A. (1991) · Brain Pathology · doi:10.1111/j.1750-3639.1991.tb00671.x · Cited by 178
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
Fischer, D., Mukrasch, M. D., Biernat, J., Bibow, S., Blackledge, M., Griesinger, C., Mandelkow, E., & Zweckstetter, M. (2009) · Biochemistry · doi:10.1021/bi901090m · Cited by 149
Tau filaments in neurodegenerative diseases
Goedert, M. (2018) · FEBS Letters · doi:10.1002/1873-3468.13108 · Cited by 127
Rat tau proteome consists of six tau isoforms: implication for animal models of human tauopathies
Hanes, J., Zilka, N., Bartkova, M., Caletkova, M., Dobrota, D., & Novak, M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05869.x · Cited by 109
Variations in filament conformation dictate seeding barrier between three- and four-repeat Tau
Dinkel, P. D., Siddiqua, A., Huynh, H., Shah, M., & Margittai, M. (2011) · Biochemistry · doi:10.1021/bi2004685 · Cited by 104
Non-motor microtubule-associated proteins
Lee, G. (1993) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(05)80013-4 · Cited by 79
Misfolded Truncated Protein τ Induces Innate Immune Response via MAPK Pathway
Kovac, A., Zilka, N., Kazmerova, Z., Cente, M., Zilkova, M., & Novak, M. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1100216 · Cited by 75
Conformational basis for asymmetric seeding barrier in filaments of three- and four-repeat tau
Siddiqua, A., Luo, Y., Meyer, V., Swanson, M. A., Yu, X., Wei, G., Zheng, J., Eaton, G. R., Ma, B., Nussinov, R., et al. (2012) · Journal of the American Chemical Society · doi:10.1021/ja303498q · Cited by 75
Folding of the Repeat Domain of Tau Upon Binding to Lipid Surfaces
Barré, P., & Eliezer, D. (2006) · Journal of Molecular Biology · doi:10.1016/j.jmb.2006.07.018 · Cited by 69
Tau-directed approaches for the treatment of Alzheimer’s disease: focus on leuco-methylthioninium
Seripa, D., Solfrizzi, V., Imbimbo, B. P., Daniele, A., Santamato, A., Lozupone, M., Zuliani, G., Greco, A., Logroscino, G., & Panza, F. (2016) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2016.1140039 · Cited by 50
Tau proteinopathies and the prion concept
(2020) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2020.08.003 · Cited by 38
Pathogenesis, Animal Models, and Drug Discovery of Alzheimer’s Disease
Xia, Z.-D., Ma, R.-X., Wen, J.-F., Zhai, Y.-F., Wang, Y.-Q., Wang, F.-Y., Liu, D., Zhao, X.-L., Sun, B., Jia, P., et al. (2023) · Journal of Alzheimer's Disease · doi:10.3233/jad-230326 · Cited by 19
Saha, D., Sun, X., Yang, W., Luo, J., & Zheng, W. (2026) · JACS Au · doi:10.1021/jacsau.6c00126 · Cited by 2
Metadata
- Authors
- Wischik, C. M., Novak, M., Edwards, P. C., Klug, A., Tichelaar, W., & Crowther, R. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1988-07
- Volume
- 85
- Issue
- 13
- Pages
- 4884-4888
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2124019813
- Cited by
- 595
- References
- 1
- FWCI
- 18.18
- Type
- journal article
- Language
- en
- Open access
- green
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