Monoclonal antibody PHF‐1 recognizes tau protein phosphorylated at serine residues 396 and 404
Abstract
The microtubule‐associated protein τ is hyperphosphorylated in the paired helical filaments (PHFs) of Alzheimer's disease. Immunological and direct chemical studies have identified Ser 396 and Ser 404 as two of the phosphorylated sites. Previously, we have demonstrated, using synthetic τ peptides containing phosphorylated Ser 396 , that this site is recognized by the monoclonal antibody PHF‐1. The present sudy extends this observation by showing that PHF‐1 recognizes τ peptides containing either individually phosphorylated Ser 396 or Ser 404 , but that there is a >10‐fold increase in the sensitivity of detection of τ peptides by PHF‐1 when both serines are phosphorylated. The recognition of singly or doubly phosphorylated Ser 396 and Ser 404 in τ by PHF‐1 can also be demonstrated in Chinese hamster ovary cells transfected with full‐length wild‐type τ constructs or mutant constructs with Ala substituted for Ser 396 or Ser 404 . We conclude that the PHF‐1 epitope contains both phosphorylated Ser 396 and Ser 404 . © 1994 Wiley‐Liss, Inc.
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High-Efficiency Transformation of Mammalian Cells by Plasmid DNA
Chen, C., & Okayama, H. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.8.2745 · Cited by 5,374 · 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-citationA68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418 · see citing works
Self-citationBramblett, 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 · see citing works
Self-citationTau protein and the neurofibrillary pathology of Alzheimer's disease
Goedert, M. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90078-z · Cited by 718 · see citing works
Self-citationA versatilein vivoandin vitroeukaryotic expression vector for protein engineering
Green, S., Issemann, I., & Sheer, E. (1988) · Nucleic Acids Research · doi:10.1093/nar/16.1.369 · Cited by 677 · see citing works
Hydrofluoric acid-treated tau PHF proteins display the same biochemical properties as normal tau.
Greenberg, S. G., Davies, P., Schein, J., & Binder, L. I. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48531-6 · Cited by 542 · see citing works
Epitopes that span the tau molecule are shared with paired helical filaments
Kosik, K. S., Orecchio, L. D., Binder, L. I., Trojanowski, J. Q., Lee, V. M.-Y., & Lee, G. S. (1988) · Neuron · doi:10.1016/0896-6273(88)90129-8 · Cited by 497 · see citing works
Self-citationLee, V., Carden, M. J., Schlaepfer, W. W., & Trojanowski, J. Q. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-11-03474.1987 · Cited by 490 · see citing works
Self-citationGoedert, M., Jakes, R., Crowther, R. A., Six, J., Lübke, U., Vandermeeren, M., Cras, P., Trojanowski, J. Q., & Lee, V. M. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.11.5066 · Cited by 446 · see citing works
Self-citationProtein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain
Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., & Ihara, Y. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41890-x · Cited by 430 · see citing works
An accurate and convenient organic phosphorus assay
McClare, C. W. F. (1971) · Analytical Biochemistry · doi:10.1016/0003-2697(71)90443-x · Cited by 426 · see citing works
In vivo phosphorylation sites in fetal and adult rat tau
Watanabe, A., Hasegawa, M., Suzuki, M., Takio, K., Morishima-Kawashima, M., Titani, K., Arai, T., Kosik, K. S., & Ihara, Y. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74447-0 · Cited by 231 · see citing works
Fetal‐Type Phosphorylation of the τ in Paired Helical Filaments
Kanemaru, K., Takio, K., Miura, R., Titani, K., & Ihara, Y. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb10039.x · Cited by 197 · see citing works
Solid phase peptide synthesis using N α -fluorenylmethoxycarbonylamino acid pentafluorophenyl esters
Atherton, E., & Sheppard, R. C. (1985) · Journal of the Chemical Society Chemical Communications · doi:10.1039/c39850000165 · Cited by 151 · see citing works
Láng, E., Szendrei, G. I., Lee, V. M. ‐., & Ötvös, L. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91264-q · Cited by 86 · see citing works
Self-citationSolid‐phase synthesis of phosphopeptides
Ötvös, L., Elekes, I., & Lee, V. M. Y. (1989) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1989.tb01501.x · Cited by 81 · see citing works
Self-citationDryland, A., & Sheppard, R. C. (1988) · Tetrahedron · doi:10.1016/s0040-4020(01)86122-6 · Cited by 54 · see citing works
Schmidt, M. L., Didario, A. G., Lee, V. M. ‐., & Trojanowski, J. Q. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00259-2 · Cited by 47 · see citing works
Self-citationTrojanowski, J. Q., Schmidt, M. L., Otvos, L. P., Arai, H., Hill, W., & Lee, V. M.-Y. (1991) · Springer eBooks · doi:10.1007/978-3-662-38445-9_10 · Cited by 18 · see citing works
Self-citationGorbics, L., Ürge, L., Láng, E., et al. (1994) · Journal of Liquid Chromatography · doi:10.1080/10826079408013443 · Cited by 8 · see citing works
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- Trojanowski JQ, 1993, From pathological marker to potential mediator of neuronal dysfunction and degeneration in Alzheimer's disease, Clin Neurosci, 1, 184
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Depletion of microglia and inhibition of exosome synthesis halt tau propagation
Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., Wolozin, B., Butovsky, O., Kügler, S., & Ikezu, T. (2015) · Nature Neuroscience · doi:10.1038/nn.4132 · Cited by 1,591 · see citing works
Soluble Amyloid β Peptide Concentration as a Predictor of Synaptic Change in Alzheimer's Disease
Lue, L.-F., Kuo, Y.-M., Roher, A. E., Brachova, L., Shen, Y., Sue, L., Beach, T., Kurth, J. H., Rydel, R. E., & Rogers, J. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65184-x · Cited by 1,530 · see citing works
Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998 · see citing works
Alonso, A. D. C., Grundke-Iqbal, I., & Iqbal, K. (1996) · Nature Medicine · doi:10.1038/nm0796-783 · Cited by 859 · see citing works
Allen, B., Ingram, E., Takao, M., Smith, M. J., Jakes, R., Virdee, K., Yoshida, H., Holzer, M., Craxton, M., Emson, P. C., et al. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09340.2002 · Cited by 746 · see citing works
“…la Recherche Médicale U422, Lille, France) and PHF1 (a kind gift from Dr. P. Davies) recognize human and murine tau phosphorylated at S396 and S404 (Otvos et al., 1994; Buée-Scherrer et al., 1996); PG5 (a kind gift from Dr. P. Davies) recognizes human and murine tau phosphorylated at S409…”
BackgroundSelf-citationTau protein and the neurofibrillary pathology of Alzheimer's disease
Goedert, M. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90078-z · Cited by 718 · see citing works
Self-citationHyperphosphorylation and aggregation of tau in mice expressing normal human tau isoforms
Andorfer, C., Kress, Y., Espinoza, M., De Silva, R., Tucker, K. L., Barde, Y., Duff, K., & Davies, P. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01879.x · Cited by 722 · see citing works
“…were used to stain free-floating brain sections: CP13 (1 : 25; Ps202; Duff et al. 2000; Lewis et al. 2000), MC1 (1 : 10; Jicha et al. 1997a, 1997b, 1999a; detecting a conformational abnormality of tau, Weaver et al. 2000), and PHF1 (1 : 25; Ps396/404; Greenberg et al. 1992; Otvos et al. 1994).”
MethodActivation of the Wnt Signaling Pathway: A Molecular Mechanism for Lithium Action
Hedgepeth, C. M., Conrad, L. J., Zhang, J., Huang, H., Lee, V. M.-Y., & Klein, P. S. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8552 · Cited by 637 · see citing works
Self-citationMonoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205
Goedert, M., Jakes, R., & Vanmechelen, E. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11484-e · Cited by 608 · see citing works
Self-citationYanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · see citing works
“PHF-1 targets a pathological form of abnormally phosphorylated tau (Otvos et al., 1994).”
InfluentialBhat, R. V., Xue, Y., von Berg, S., Hellberg, S., Ormö, M., Nilsson, Y., Radesäter, A., Jerning, E., Markgren, P.-O., Borgegård, T., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306268200 · Cited by 557 · see citing works
Wang, J., Xia, Y., Grundke, I., & Iqbal, K. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129031 · Cited by 530 · see citing works
“In transgenic mouse models expressing human tau, the presence of tau filaments did not correlate directly with the death of individual neurons [138–199] and furthermore, formation of tau filaments seems neuroprotective [140, 141].”
BackgroundMolecular Targets of Lithium Action
Phiel, C. J., & Klein, P. S. (2001) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.41.1.789 · Cited by 516 · see citing works
Cell-cycle reentry and cell death in transgenic mice expressing nonmutant human tau isoforms
Andorfer, C., Acker, C. M., Kress, Y., Hof, P. R., Duff, K., & Davies, P. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4637-04.2005 · Cited by 511 · see citing works
“1B) resembled reactivity of these antibodies to NFTs from human brain (Fig.”
BackgroundInfluentialAsuni, A. A., Boutajangout, A., Quartermain, D., & Sigurdsson, E. M. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2361-07.2007 · Cited by 506 · see citing works
Ishihara, T., Hong, M., Zhang, B., Nakagawa, Y., Lee, M. K., Trojanowski, J. Q., & Lee, V. M.-Y. (1999) · Neuron · doi:10.1016/s0896-6273(00)81127-7 · Cited by 564 · see citing works
Self-citationLithium Reduces Tau Phosphorylation by Inhibition of Glycogen Synthase Kinase-3
Hong, M., Chen, D. C. R., Klein, P. S., & Lee, V. M. ‐. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.40.25326 · Cited by 470 · see citing works
Self-citationNeuropathologic substrates of Parkinson disease dementia
Irwin, D. J., White, M. T., Toledo, J. B., Xie, S. X., Robinson, J. L., Van Deerlin, V., Lee, V. M. ‐., Leverenz, J. B., Montine, T. J., Duda, J. E., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23659 · Cited by 518 · see citing works
Self-citationVincent, I. J., Jicha, G. A., Rosado, M., & Dickson, D. W. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-10-03588.1997 · Cited by 444 · see citing works
“Under these conditions, every one of the kinases produced the PHF-1 phospho-epitope, which contains a proline-directed serine residue at position 396 of tau (Otvos et al., 1994), but is not M-phase-specific (Vincent et al., 1996).”
BackgroundGötz, J., Probst, A., Spillantini, M. G., Schäfer, T., Jakes, R., Bürki, K., & Goedert, M. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07116.x · Cited by 441 · see citing works
Self-citationGong, C.-X., Lidsky, T., Wegiel, J., Zuck, L., Grundke-Iqbal, I., & Iqbal, K. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.8.5535 · Cited by 405 · see citing works
Histone deacetylase 6 interacts with the microtubule‐associated protein tau
Ding, H., Dolan, P. J., & Johnson, G. V. W. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05564.x · Cited by 387 · see citing works
Planel, E., Richter, K. E. G., Nolan, C. E., Finley, J. E., Liu, L., Wen, Y., Krishnamurthy, P., Herman, M., Wang, L., Schachter, J. B., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4854-06.2007 · Cited by 386 · see citing works
“…antibodies (specificity given in parentheses) were a generous gift from Dr. Peter Davies (Albert Einstein University, New York, NY): TG-3, phospho-Ser231 and conformation specific (Jicha et al., 1997); MC-6, phospho-Ser235 (Jicha et al., 1997); and PHF-1, phospho-Ser396/404 (Otvos et al., 1994).”
BackgroundSpittaels, K., den Haute, C. V., Dorpe, J. V., Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., Mercken, M., Sciot, R., Lommel, A. V. V., et al. (1999) · American Journal of Pathology · doi:10.1016/s0002-9440(10)65533-2 · Cited by 405 · see citing works
Phosphorylated 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
Leroy, K., Yilmaz, Z., & Brion, J. ‐. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2006.00795.x · Cited by 404 · see citing works
Axonopathy and amyotrophy in mice transgenic for human four-repeat tau protein
Probst, A., Götz, J., Wiederhold, K., Tolnay, M., Mistl, C., Jaton, A., Hong, M., Ishihara, T., Lee, V., Trojanowski, J., et al. (2000) · Acta Neuropathologica · doi:10.1007/s004010051148 · Cited by 362 · see citing works
Self-citationPassive Immunization with Anti-Tau Antibodies in Two Transgenic Models
Chai, X., Wu, S., Murray, T. K., Kinley, R. D., Cella, C. V., Sims, H., Buckner, N., Hanmer, J. M., Davies, P., O’Neill, M. J., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.229633 · Cited by 350 · see citing works
Spillantini, M. G., Goedert, M., Crowther, R. A., Murrell, J. R., Farlow, M. R., & Ghetti, B. F. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4113 · Cited by 334 · see citing works
Self-citationDemars, M., Hu, Y., Gadadhar, A., & Lazarov, O. (2010) · Journal of Neuroscience Research · doi:10.1002/jnr.22387 · Cited by 326 · see citing works
Moloney, C. M., Lowe, V. J., & Murray, M. E. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12321 · Cited by 337 · see citing works
Age-Dependent Impairment of Cognitive and Synaptic Function in the htau Mouse Model of Tau Pathology
Polydoro, M., Acker, C. M., Duff, K., Castillo, P. E., & Davies, P. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1065-09.2009 · Cited by 329 · see citing works
“The following monoclonal antibodies were used to stain free-floating brain sections: CP13 [1:5000; Ps202 (Duff et al., 2000; Lewis et al., 2000)] and PHF1 [1:5000; Ps396/404 (Greenberg et al., 1992; Otvos et al., 1994)].”
BackgroundMethodGBP, an Inhibitor of GSK-3, Is Implicated in Xenopus Development and Oncogenesis
Yost, C., Farr, G. H., Pierce, S. B., Ferkey, D. M., Chen, M. M., & Kimelman, D. (1998) · Cell · doi:10.1016/s0092-8674(00)81208-8 · Cited by 328 · see citing works
Lithium inhibits Alzheimer's disease‐like tau protein phosphorylation in neurons
Muñoz-Montaño, J. R., Moreno, F. J., Ávila, J., & Díaz‐Nido, J. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)00688-1 · Cited by 322 · see citing works
Spittaels, K., den Haute, C. V., Dorpe, J. V., Geerts, H., Mercken, M. H., Bruynseels, K., Lasrado, R., Vandezande, K., Laenen, I., Boon, T., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006219200 · Cited by 317 · see citing works
Microtubule-associated protein tau is essential for long-term depression in the hippocampus
Kimura, T., Whitcomb, D. J., Jo, J., Regan, P., Piers, T., Heo, S., Brown, C., Hashikawa, T., Murayama, M., Seok, H., et al. (2014) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2013.0144 · Cited by 307 · see citing works
An, W.-L., Cowburn, R. F., Li, L., Braak, H., Alafuzoff, I., Iqbal, K., Iqbal, I.-G., Winblad, B., & Pei, J.-J. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63687-5 · Cited by 312 · see citing works
Conformational change as one of the earliest alterations of tau in Alzheimer's disease
Weaver, C. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00157-3 · Cited by 310 · see citing works
Boutajangout, A., Ingadottir, J., Davies, P., & Sigurdsson, E. M. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07337.x · Cited by 306 · see citing works
Illenberger, S., Zheng‐Fischhöfer, Q., Preuß, U., Stamer, K., Baumann, K., Trinczek, B., Biernat, J., Godemann, R., Mandelkow, E., & Mandelkow�, E. (1998) · Molecular Biology of the Cell · doi:10.1091/mbc.9.6.1495 · Cited by 300 · see citing works
“Among the identified phosphopeptides, only four (T181, S202/T205*, T231/S235, and S396/S404) would be detected immunocytochemically with the monoclonal antibodies AT270, AT8, AT180, and PHF-1, respectively (Biernat et al., 1992; Goedert et al., 1995).”
BackgroundInfluentialDetection of Phosphorylated Ser262 in Fetal Tau, Adult Tau, and Paired Helical Filament Tau
Seubert, P., Mawal-Dewan, M., Barbour, R., Jakes, R., Goedert, M., Johnson, G. V. W., Litersky, J. M., Schenk, D., Lieberburg, I., Trojanowski, J. Q., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18917 · Cited by 345 · see citing works
Self-citationPERK inhibition prevents tau-mediated neurodegeneration in a mouse model of frontotemporal dementia
Radford, H. E., Moreno, J. A., Verity, N., Halliday, M., & Mallucci, G. R. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1487-z · Cited by 289 · see citing works
“A number of different antibodies have been described that recognise different tau phosphorylation sites and pathology, including AT8 [10, 22], which detects phosphorylation at Ser/Thr and is a marker for pretangles and tangles, and PHF1 [28], which detects late-stage tangles including tau phosphorylated at Ser.”
BackgroundJeganathan, S., Hascher, A., Chinnathambi, S., Biernat, J., Mandelkow, E.-M., & Mandelkow, E. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805300200 · Cited by 278 · see citing works
Cho, J., & Johnson, G. V. W. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02155.x · Cited by 282 · see citing works
Ghetti, B. F., Piccardo, P., Spillantini, M. G., Ichimiya, Y., Porro, M., Perini, F., Kitamoto, T., Tateishi, J., Seiler, C. E., Frangione, B., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.2.744 · Cited by 281 · see citing works
Self-citationAcetylated 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 · see citing works
Self-citationMondragón‐Rodríguez, S., Perry, G. L., Luna‐Muñoz, J., Acevedo, M., & Williams, S. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12084 · Cited by 276 · see citing works
Immunotherapy Targeting Pathological Tau Prevents Cognitive Decline in a New Tangle Mouse Model
Boutajangout, A., Quartermain, D., & Sigurdsson, E. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4363-10.2010 · Cited by 272 · see citing works
“…(1) mouse monoclonal tau antibodies that stain pathological tau PHF1 [1:1000, recognizes phosphorylated serines 396 and 404 of tau protein (Otvos et al., 1994), and shows only minimal axonal staining in normal human brain, generously provided by Peter Davies (Albert Einstein College of…”
BackgroundLithium protects cultured neurons against β‐amyloid‐induced neurodegeneration
Alvarez, G., Muñoz-Montaño, J. R., Satrústegui, J., Ávila, J., Bogónez, E., & Díaz‐Nido, J. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00685-7 · Cited by 270 · see citing works
Jicha, G. A., Lane, E., Vincent, I. J., Ötvös, L., Hoffmann, R., & Davies, P. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69052087.x · Cited by 264 · see citing works
Boluda, S., Iba, M., Zhang, B., Raible, K. M., Lee, V. M. ‐., & Trojanowski, J. Q. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1373-0 · Cited by 259 · see citing works
“The same samples were analyzed by immunoblotting using anti-tau antibodies that recognize a phosphorylation-independent anti-tau polyclonal antibody raised to recombinant tau (17025, 1:2,000; produced in the Penn Center for Neurodegenerative Disease Research (CNDR); [52]) and PHF tau phosphorylated at Ser 396/404 (mon…”
Self-citationEngel, T., Hernández, F., Ávila, J., & Lucas, J. J. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.0604-06.2006 · Cited by 261 · see citing works
Theunis, C., Crespo-Biel, N., Gafner, V., Pihlgren, M., López-Deber, M. P., Reis, P., Hickman, D. T., Adolfsson, O., Chuard, N., Ndao, D. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072301 · Cited by 259 · see citing works
“AD2 and PHF1 among others, are located in this region [25–29].”
BackgroundTau immunotherapy for Alzheimer's disease
Pedersen, J. T., & Sigurdsson, E. M. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.03.003 · Cited by 247 · see citing works
Glycogen Synthase Kinase 3β Phosphorylates Tau at Both Primed and Unprimed Sites
Cho, J.-H., & Johnson, G. V. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m206236200 · Cited by 266 · see citing works
miR-132/212 deficiency impairs tau metabolism and promotes pathological aggregation in vivo
Smith, P. Y., Hernandez-Rapp, J., Jolivette, F., Lecours, C., Bisht, K., Goupil, C., Dorval, V., Parsi, S., Morin, F., Planel, E., et al. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv377 · Cited by 233 · see citing works
“Antibodies directed against tau include: AT8 (Ser202/Thr205, ThermoFisher), PHF-1 [Ser396/Ser404, (87)], phosphoSer422 (#OPA-03151; ThermoScientific), CP27 (specific to human total tau) and total tau (A0024, Dako Cytomation).”
BackgroundDeng, Y., Li, B., Liu, Y. M., Iqbal, K., Grundke, I., & Gong, C. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.090157 · Cited by 233 · see citing works
Williamson, R., Scales, T., Clark, B. R., Gibb, G., Reynolds, C. H., Kellie, S., Bird, I. N., Varndell, I. M., Sheppard, P. W., Everall, I., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-01-00010.2002 · Cited by 227 · see citing works
“The labeling by 4G10 was weaker than PHF-1, and it was found to be necessary to enrich for PHF-tau to observe clear labeling by 4G10, suggesting that the phosphotyrosine content is lower than the level of phosphorylation at the PHF-1 epitope (serines 396 and 404) (Otvos et al., 1994).”
BackgroundUp-regulation of inhibitors of protein phosphatase-2A in Alzheimer’s disease
Tanimukai, H., Grundke-Iqbal, I., & Iqbal, K. (2005) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)62486-8 · Cited by 220 · see citing works
P38 MAP kinase is activated at early stages in Alzheimer's disease brain
Sun, A. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00180-8 · Cited by 219 · see citing works
Olfactory epithelium amyloid‐β and paired helical filament‐tau pathology in Alzheimer disease
Arnold, S. E., Lee, E. B., Moberg, P. J., Stutzbach, L., Kazi, H., Han, L., Lee, V. M. ‐., & Trojanowski, J. Q. (2009) · Annals of Neurology · doi:10.1002/ana.21910 · Cited by 215 · see citing works
Self-citationSpecificity and Regulation of Casein Kinase-Mediated Phosphorylation of ??-Synuclein
Waxman, E. A., & Giasson, B. I. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3186fc995 · Cited by 232 · see citing works
Proapoptotic Effects of Tau Cleavage Product Generated by Caspase-3
Chung, C.-W., Song, Y.-H., Kim, I.-K., Yoon, W. J., Ryu, B. R., Jo, D., Woo, H., Kwon, Y.-K., Kim, H., Gwag, B.-J., et al. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2000.0335 · Cited by 211 · see citing works
Dayanandan, R., van Slegtenhorst, M., Mack, T. G. A., Ko, L., Yen, S. H., Leroy, K., Brion, J., Anderton, B. H., Hutton, M. L., & Lovestone, S. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)00222-7 · Cited by 210 · see citing works
cAMP-Dependent Protein Kinase Phosphorylations on Tau in Alzheimer’s Disease
Jicha, G. A., Weaver, C. L., Lane, E., Vianna, C., Kress, Y., Rockwood, J. M., & Davies, P. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-17-07486.1999 · Cited by 207 · see citing works
Tau Phosphorylation at Serine 396 Residue Is Required for Hippocampal LTD
Regan, P., Piers, T., Yi, J.-H., Kim, D.-H., Huh, S., Park, S. J., Ryu, J. H., Whitcomb, D. J., & Cho, K. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.2842-14.2015 · Cited by 202 · see citing works
“…(Zhu et al., 2002; Peineau et al., 2007; Kimura et al., 2014), using the antibodies PHF-1 (an antibody that recognizes phosphorylation at residues S396 and S404 of tau; Otvos et al., 1994) and AT8 (an antibody that recognizes phosphorylation at S202 and T205 residues of tau; Goedert et al., 1995).”
MethodGlycogen synthase kinase-3β phosphorylates tau protein at multiple sites in intact cells
Sperbera, B. R., Leight, S., Goedert, M., & Lee, V. M.-Y. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11902-9 · Cited by 204 · see citing works
Self-citationLim, F., Hernández, F., Lucas, J., Gómez-Ramos, P., Morán, M., & Ávila, J. (2001) · Molecular and cellular neurosciences · doi:10.1006/mcne.2001.1051 · Cited by 215 · see citing works
Brion, J., Tremp, G. L., & Octave, J. (1999) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65272-8 · Cited by 197 · see citing works
Ibuprofen reduces Aβ, hyperphosphorylated tau and memory deficits in Alzheimer mice
McKee, A. C., Carreras, I., Hossain, L., Ryu, H., Klein, W. L., Oddo, S., LaFerla, F. M., Jenkins, B. G., Kowall, N. W., & Dedeoglu, A. (2008) · Brain Research · doi:10.1016/j.brainres.2008.01.095 · Cited by 196 · see citing works
Waxman, E. A., & Giasson, B. I. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0297-11.2011 · Cited by 193 · see citing works
“Intracellular localization of these pathological aggregates can be identified in these disorders, primarily composed of tau-forming neurofibrilliary tangles (NFTs) in AD or of -synuclein ( -syn)-forming Lewy pathology in PD.”
BackgroundInfluentialLong-Term In Vivo Imaging of Fibrillar Tau in the Retina of P301S Transgenic Mice
Schön, C., Hoffmann, N. A., Ochs, S. M., Burgold, S., Filser, S., Steinbach, S., Seeliger, M. W., Arzberger, T., Goedert, M., Kretzschmar, H. A., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0053547 · Cited by 192 · see citing works
“After blocking 30 min with Casein-I, probes were stained with antibodies against hyperphosphorylated tau (AT8, 1:200; AT100, 1:200; AT180, 1:50, Thermo Scientific, product #MN1040; AT270, 1:200, Thermo Scientific, product # MN1050 or PHF-1, 1:1000 [25]) and Ab (4G8, 1:1000; Table 1.”
MethodSelf-citationQuantification of Axonal Damage in Traumatic Brain Injury
Zemlan, F. P., Rosenberg, W. S., Luebbe, P., Campbell, T. A., Dean, G. E., Weiner, N. E., Cohen, J. A., Rudick, R. A., & Woo, D. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720741.x · Cited by 187 · see citing works
“This fragment could also be labeled with the Mab PHF-1, which recognizes phosphorylated Ser of tau (Otvos et al., 1994; Zemlan and Dean, 1996).”
BackgroundPick's disease: hyperphosphorylated tau protein segregates to the somatoaxonal compartment
Probst, A., Tolnay, M., Langui, D., Goedert, M., & Spillantini, M. G. (1996) · Acta Neuropathologica · doi:10.1007/s004010050565 · Cited by 188 · see citing works
Self-citationBennecib, M., Gong, C.-X., Grundke-Iqbal, I., & Iqbal, K. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)02203-1 · Cited by 184 · see citing works
Hamilton, R. H., Patel, S. V., Lee, E. B., Jackson, E. M., Lopinto, J., Arnold, S. E., Clark, C. M., Basil, A. K., Shaw, L. M. J., Xie, S. X., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22015 · Cited by 187 · see citing works
Tau Phosphorylation Sites Work in Concert to Promote Neurotoxicity In Vivo
Steinhilb, M. L., Dias-Santagata, D., Fulga, T. A., Felch, D. L., & Feany, M. B. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e07-04-0327 · Cited by 187 · see citing works
“Using disease-associated phospho-specific antibodies to analyze the phosphorylation status of tau AP5 , we found that reactivity with AT270, PHF1, and Tau1 was unchanged compared with tau WT (Figure 6C).”
InfluentialMutant valosin‐containing protein causes a novel type of frontotemporal dementia
Schröder, R., Watts, G. D. J., Mehta, S. G., Evert, B. O., Broich, P., Fließbach, K., Pauls, K., Hans, V. H., Kimonis, V., & Thal, D. R. (2005) · Annals of Neurology · doi:10.1002/ana.20407 · Cited by 177 · see citing works
The role of tau kinases in Alzheimer's disease.
Dolan, P. J., & Johnson, G. V. W. (2010) · PubMed · Cited by 174 · see citing works
Sayas, C. L., Moreno-Flores, M. T., Ávila, J., & Wandosell, F. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.52.37046 · Cited by 172 · see citing works
Amyloid-β signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer's disease
Seward, M. E., Swanson, E., Norambuena, A., Reimann, A., Cochran, J. N., Li, R., Roberson, E. D., & Bloom, G. S. (2013) · Journal of Cell Science · doi:10.1242/jcs.1125880 · Cited by 170 · see citing works
“…CCR, have not been regarded as canonical AD phospho- tau sites, such as those recognized by the monoclonal antibodies, PHF-1 (pS396/pS404) (Otvos et al., 1994), AT8 (S199/pS202/ pS205) (Porzig et al., 2007), AT100 (pT212/pS214) (Zheng- Fischhöfer et al., 1998) or AT180 (pT231/pS235)…”
BackgroundSun, L., Liu, S. Y., Zhou, X. W., Wang, X. C., Liu, R., Wang, Q., & Wang, J. Z. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00697-8 · Cited by 168 · see citing works
Hu, Y., Xu, P., Pigino, G. F., Brady, S. T., Larson, J., & Lazarov, O. (2010) · The FASEB Journal · doi:10.1096/fj.09-136945 · Cited by 168 · see citing works
Role of glycosylation in hyperphosphorylation of tau in Alzheimer's disease
Liu, F., Zaidi, T., Iqbal, K., Grundke-Iqbal, I., Merkle, R. K., & Gong, C.-X. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02228-7 · Cited by 167 · see citing works
Lee, G. S., & Leugers, C. J. (2012) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-385883-2.00004-7 · Cited by 166 · see citing works
Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice
Ojo, J.-O., Mouzon, B., Greenberg, M. B., Bachmeier, C., Mullan, M., & Crawford, F. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3182814cdf · Cited by 166 · see citing works
Lithium and valproic acid: parallels and contrasts in diverse signaling contexts
Gurvich, N. (2002) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00299-1 · Cited by 162 · see citing works
“In addition to MAP-1B, GSK-3b also phosphorylates the MAP tau (Lee, 1995; Lovestone et al., 1994; Mandelkow & Mandelkow, 1993; Otvos et al., 1994).”
BackgroundAlonso, A. D. C., Zaidi, T., Novák, M., Barra, H. S., Grundke, I., & Iqbal, K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105365200 · Cited by 160 · see citing works
Serrano-Pozo, A., William, C. M., Ferrer, I., Uro-Coste, E., Delisle, M.-B., Maurage, C.-A., Hock, C., Nitsch, R. M., Masliah, E., Growdon, J. H., et al. (2010) · Brain · doi:10.1093/brain/awq056 · Cited by 159 · see citing works
Casein Kinase 1 Delta Phosphorylates Tau and Disrupts Its Binding to Microtubules
Li, G., Yin, H., & Kuret, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314116200 · Cited by 159 · see citing works
Chiasseu, M., Alarcón-Martínez, L., Belforte, N., Quintero, H., Dotigny, F., Destroismaisons, L., Velde, C. V., Panayi, F., Louis, C., & Polo, A. D. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0199-3 · Cited by 158 · see citing works
TauGene Mutation K257T Causes a Tauopathy Similar to Pick's Disease
Rizzini, C., Goedert, M., Hodges, J. R., Smith, M. J., Jakes, R., Hills, R., Xuereb, J. H., Crowther, R. A., & Spillantini, M. G. (2000) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/59.11.990 · Cited by 159 · see citing works
“AT100 recognizes tau phosphorylated at T212 and S214 (38), AT180 recognizes tau phosphorylated at T231 (39), 12E8 recognizes tau phosphorylated at S262 and/ or S356 (40), PHF1 recognizes tau phosphorylated at S396 and S404 (41) and AP422 recognizes tau phosphorylated at S422 (42).”
BackgroundSelf-citationTissue-nonspecific Alkaline Phosphatase Promotes the Neurotoxicity Effect of Extracellular Tau
Dı́az-Hernández, M., Gómez‐Ramos, A., Rubio, A., Gómez‐Villafuertes, R., Naranjo, J. R., Miras‐Portugal, M. T., & Ávila, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.145003 · Cited by 155 · see citing works
Activation of Caspase-6 in Aging and Mild Cognitive Impairment
Albrecht, S., Bourdeau, M., Bennett, D. A., Mufson, E. J., Bhattacharjee, M. B., & LeBlanc, A. C. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060974 · Cited by 155 · see citing works
Reduction of Nuak1 Decreases Tau and Reverses Phenotypes in a Tauopathy Mouse Model
Lasagna‐Reeves, C. A., de Haro, M., Hao, S., Park, J., Rousseaux, M. W. C., Al‐Ramahi, I., Jafar‐Nejad, P., Vilanova-Velez, L., See, L., Maio, A. D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.022 · Cited by 156 · see citing works
Buée‐Scherrer, V., Condamines, O., Mourton-Gilles, C., Jakes, R., Goedert, M., Pau, B., & Delacourte, A. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(96)00003-4 · Cited by 155 · see citing works
“They allowed for the identif i c a t i o n o f a b n o r m a l l y p h o s p h o r y l a t e d sites [20] [21] [23] [28] [35] [42].”
BackgroundSelf-citationTauopathy with paired helical filaments in an aged chimpanzee
Rosen, R. F., Farberg, A. S., Gearing, M., Dooyema, J., M. Long, P., Anderson, D. C., Davis‐Turak, J., Coppola, G., Geschwind, D. H., Paré, J., et al. (2008) · Journal of Comparative Neurology · doi:10.1002/cne.21744 · Cited by 153 · see citing works
“Specificity was confirmed with Western blots of transfected cell lysates (Otvos et al., 1994).”
BackgroundMethodInfluentialLi, L., Sengupta, A., Haque, N., Grundke, I., & Iqbal, K. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.04.047 · Cited by 151 · see citing works
PKA modulates GSK‐3β‐ and cdk5‐catalyzed phosphorylation of tau in site‐ and kinase‐specific manners
Liu, F., Liang, Z., Shi, J., Yin, D., El-Akkad, E., Grundke, I., Iqbal, K., & Gong, C. (2006) · FEBS Letters · doi:10.1016/j.febslet.2006.10.033 · Cited by 149 · see citing works
“phosphorylated Ser396 than to phosphorylated Ser404 of tau [26].”
BackgroundTransgenic Mouse Model of Tauopathies with Glial Pathology and Nervous System Degeneration
Higuchi, M., Ishihara, T., Zhang, B., Hong, M., Andreadis, A., Trojanowski, J. Q., & Lee, V. M. ‐. (2002) · Neuron · doi:10.1016/s0896-6273(02)00789-4 · Cited by 149 · see citing works
“Otvos et al., 1994); mAb PHF6 (Hoffmann et al., 1997); mAb AT8 D’Souza, I., Poorkaj, P., Hong, M., Nochlin, D., Lee, V.M.-Y., Bird,(Goedert et al., 1994; Matsuo et al., 1994); mAb AT270 (Goedert et T.D., and Schellenberg, G.D. (1999).”
Self-citation
- Authors
- Otvos, L., Feiner, L., Lang, E., Szendrei, G. I., Goedert, M., & Lee, V. M.
- Affiliations
- The Wistar Institute (US)
- University of Pennsylvania (US)
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Otvos, L.
- ORCID
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 1994-12-15
- Volume
- 39
- Issue
- 6
- Pages
- 669-673
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W1984482388
- Semantic Scholar
- 4518f282e57a4d29fb281b9a658ed49720534f5d
- Cited by
- 488
- References
- 21
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 14 · 2023: 11 · 2022: 13 · 2021: 11 · 2020: 13 · 2019: 13 · 2018: 6 · 2017: 13 · 2016: 16 · 2015: 12 · 2014: 7 · 2013: 24 · 2012: 23
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag010670-02, 5p01ag009215-20)
- National Institute on Aging (AG09215, AG 10670)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau protein, tau hyperphosphorylation, paired helical filaments, Alzheimer's disease, epitope mapping, CHO cells
- MeSH terms
- Alzheimer Disease, Amino Acid Sequence, Animals, Antibodies, Monoclonal, Epitopes, Enzyme-Linked Immunosorbent Assay, Cricetinae, Humans, Molecular Sequence Data, Peptides, Phosphorylation, Serine, Blotting, Western, CHO Cells, tau Proteins, DNA, Complementary
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