Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice
Abstract
As an abnormally folded and aggregated protein, tau composed of neurofibrillary tangles (NFTs) in Alzheimer's disease and other tauopathies seems to be a candidate for immunotherapy. Yet, the encephalitogenicity of full-length tau protein, recently reported by us in immunized mice, demands to carefully and selectively target pathological tau and address both efficacy (anti-NFT effect) and safety (free of encephalitis). We immunized NFT mice with NFT-related phosphorylated (phos) tau peptides, using an immunization protocol aimed to predispose a proinflammatory milieu in CNS as a set up to detect biohazard, an approach we used when the neurotoxicity of full-length tau was detected [use of complete Freund adjuvant (CFA) with pertussis toxin (PT)]. A decrease of about 40% in NFT burden in CNS was demonstrated and was accompanied with an increase in microglial burden. Anti-phos-tau antibodies were detected in serum and blood vessels in the CNS, while no encephalitogenicity (free of clinical neurological deficits, of adverse effects on brain inflammatory cells and of axonal damage) was recorded. The level of the lysosomal proteases, cathepsins D and L, was affected in the immunized mice suggesting the possible involvement of the lysosomal system in the decrease of NFTs. The robust anti-NFT effect and the lack of encephalitogenicity in NFT mice immunized with phos-tau peptides, even though CFA with PT was included in vaccine, point to their anti-NFT therapeutic potential.
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Active tau immunization reduces tau pathology by targeting single or multiple phospho-epitopes, the amino terminus, full-length normal and mutant tau, or aggregated tau.
“Active tau immunization has been shown to reduce tau pathology by targeting single185, 187, 189–193 or multiple194 phospho-epitopes, the amino terminus195, full-length normal and mutant tau196, 197, or aggregated tau198.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [194]
Similar tau immunogens administered with a milder adjuvant or fewer immunizations do not produce such adverse reactions.
“Similar tau immunogens administered with a milder adjuvant or fewer immunizations do not produce such adverse reactions194,196”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [194]
Cites
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
Holmes, C., Boche, D., Wilkinson, D., Yadegarfar, G., Hopkins, V., Bayer, A., Jones, R. W., Bullock, R., Love, S., Neal, J. W., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61075-2 · Cited by 1,416 · see citing works
Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: a case report
Nicoll, J. A. R., Wilkinson, D., Holmes, C., Steart, P., Markham, H., & Weller, R. O. (2003) · Nature Medicine · doi:10.1038/nm840 · Cited by 1,397 · see citing works
Subacute meningoencephalitis in a subset of patients with AD after Aβ42 immunization
Orgogozo, J.-M., Gilman, S., Dartigues, J.-F., Laurent, B., Puel, M., Kirby, L. C., Jouanny, P., Dubois, B., Eisner, L., Flitman, S., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000073623.84147.a8 · Cited by 1,356 · see citing works
Classification and basic pathology of Alzheimer disease
Duyckaerts, C., Delatour, B., & Potier, M.-C. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0532-1 · Cited by 1,031 · see citing works
Oddo, S., Billings, L., Kesslak, J. P., Cribbs, D. H., & LaFerla, F. M. (2004) · Neuron · doi:10.1016/j.neuron.2004.07.003 · Cited by 780 · see citing works
Kitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N., & LaFerla, F. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2868-05.2005 · Cited by 697 · see citing works
Rapamycin alleviates toxicity of different aggregate-prone proteins
Berger, Z., Ravikumar, B., Menzies, F. M., Oroz, L. G., Underwood, B. R., Pangalos, M. N., Schmitt, I., Wullner, U., Evert, B. O., O'Kane, C. J., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddi458 · Cited by 657 · see citing works
Tau fragmentation, aggregation and clearance: the dual role of lysosomal processing
Wang, Y., Martinez-Vicente, M., Krüger, U., Kaushik, S., Wong, E., Mandelkow, E.-M., Cuervo, A. M., & Mandelkow, E. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp367 · Cited by 617 · see citing works
Monoclonal 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
Ferrer, I., Boada, M., Guerra, M. L. S., Rey, M. J., & Costa‐Jussà, F. R. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00493.x · Cited by 567 · see citing works
Li, Y., Liu, L., Barger, S. W., & Griffin, W. S. T. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-05-01605.2003 · Cited by 563 · see citing works
Effects of α-Synuclein Immunization in a Mouse Model of Parkinson’s Disease
Masliah, E., Rockenstein, E., Adame, A., Alford, M., Crews, L., Hashimoto, M., Seubert, P., Lee, M., Goldstein, J., Chilcote, T., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.010 · Cited by 542 · see citing works
Asuni, 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
Silver staining of Alzheimer's neurofibrillary changes by means of physical development.
Gallyas, F. (1971) · PubMed · Cited by 411 · see citing works
Mercken, M. H., Vandermeeren, M., Lübke, U., Six, J., Boons, J., VOORDE, A. V. D., Martin, J., & Gheuens, J. (1992) · Acta Neuropathologica · doi:10.1007/bf00227819 · Cited by 356 · see citing works
Aβ vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease
Masliah, E., Hansen, L., Adame, A., Crews, L. A., Bard, F., Lee, C., Seubert, P. A., Games, D., Kirby, L., & Schenk, D. (2005) · Neurology · doi:10.1212/01.wnl.0000148590.39911.df · Cited by 355 · see citing works
Zheng‐Fischhöfer, Q., Biernat, J., Mandelkow, E., Illenberger, S., Godemann, R., & Mandelkow�, E. (1998) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1998.2520542.x · Cited by 322 · see citing works
Dalmau, J. O., Furneaux, H., Rosenblum, M. K., Graus, F., & Posner, J. B. (1991) · Neurology · doi:10.1212/wnl.41.11.1757 · Cited by 219 · see citing works
Ishizawa, K., & Dickson, D. W. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.6.647 · Cited by 209 · see citing works
Kenessey, Á., Nacharaju, P., Ko, L., & Yen, S. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69052026.x · Cited by 191 · see citing works
Tauopathy-like Abnormalities and Neurologic Deficits in Mice Immunized With Neuronal Tau Protein
Rosenmann, H., Grigoriadis, N., Karussis, D., Boimel, M., Touloumi, O., Ovadia, H., & Abramsky, O. (2006) · Archives of Neurology · doi:10.1001/archneur.63.10.1459 · Cited by 178 · see citing works
Self-citationMonsonego, A., Imitola, J., Petrovic, S., Zota, V. E., Nemirovsky, A., Baron, R., Fisher, Y., Owens, T., & Weiner, H. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506209103 · Cited by 159 · see citing works
Autophagy-mediated clearance of aggresomes is not a universal phenomenon
Wong, E. S. P., Tan, J. M. M., Soong, W.-E., Hussein, K., Nukina, N., Dawson, V. L., Dawson, T. M., Cuervo, A. M., & Lim, K. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn157 · Cited by 157 · see citing works
Elliott, E., Atlas, R., Lange, A. A., & Ginzburg, I. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04290.x · Cited by 142 · see citing works
Neuronal and microglial cathepsins in aging and age-related diseases
Nakanishi, H. (2003) · Ageing Research Reviews · doi:10.1016/s1568-1637(03)00027-8 · Cited by 128 · see citing works
Tampellini, D., Magrané, J., Takahashi, R. H., Li, F., Lin, M. T., Almeida, C. G., & Gouras, G. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m700373200 · Cited by 118 · see citing works
Vaccination with amyloid-beta peptide induces autoimmune encephalomyelitis in C57/BL6 mice
Furlan, R. (2003) · Brain · doi:10.1093/brain/awg031 · Cited by 116 · see citing works
Shein, N. A., Grigoriadis, N., Alexandrovich, A. G., Simeonidou, C., Lourbopoulos, A. I., Polyzoidou, E., Trembovler, V., Mascagni, P., Dinarello, C. A., & Shohami, E. (2009) · The FASEB Journal · doi:10.1096/fj.09-134700 · Cited by 98 · see citing works
Self-citationIntraneuronal IgG in the central nervous system
Fabian, R. H., & Petroff, G. (1987) · Neurology · doi:10.1212/wnl.37.11.1780 · Cited by 97 · see citing works
Rosenmann, H., Grigoriadis, N., Eldar-Levy, H., Avital, A., Rozenstein‐Tsalkovich, L., Touloumi, O., Behar, L., Ben‐Hur, T., Avraham, Y., Berry, E., et al. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.03.007 · Cited by 93 · see citing works
Self-citationStatins reduce the neurofibrillary tangle burden in a mouse model of tauopathy
Boimel, M., Grigoriadis, N., Lourbopoulos, A., Touloumi, O., Rosenmann, D., Abramsky, O., & Rosenmann, H. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31819ac3cb · Cited by 86 · see citing works
Self-citationWilms, H., Hartmann, D., & Sievers, J. (1997) · Cell and Tissue Research · doi:10.1007/s004410050769 · Cited by 86 · see citing works
Rosenmann, H., Meiner, Z., Geylis, V., Abramsky, O., & Steinitz, M. (2006) · Neuroscience Letters · doi:10.1016/j.neulet.2006.01.072 · Cited by 77 · see citing works
Self-citationKaye, J. F., de Rosbo, N. K., Mendel, I., Flechter, S., Hoffman, M. A., Yust, I., & Ben‐Nun, A. (2000) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00168-x · Cited by 72 · see citing works
Are the Extracelluar Pathways a Conduit for the Delivery of Therapeutics to the Brain?
Banks, W. A. (2004) · Current Pharmaceutical Design · doi:10.2174/1381612043384862 · Cited by 58 · see citing works
Amelioration of autoimmune neuroinflammation by recombinant human alpha-fetoprotein
Irony-Tur-Sinai, M., Grigoriadis, N., Lourbopoulos, A. I., Pinto-Maaravi, F., Abramsky, O., & Brenner, T. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2005.11.012 · Cited by 47 · see citing works
Self-citationPhosphorylation of Tau Alters Its Association with the Plasma Membrane
Ekinci, F. J., & Shea, T. B. (2000) · Cellular and Molecular Neurobiology · doi:10.1023/a:1007075115574 · Cited by 45 · see citing works
Uptake of antineuronal IgM by CNS neurons
Fabian, R. H. (1990) · Neurology · doi:10.1212/wnl.40.3_part_1.419 · Cited by 38 · see citing works
Inhibition of Autophagy Causes Tau Proteolysis by Activating Calpain in Rat Brain
Zhang, J. Y., Peng, C., Shi, H., Wang, S., Wang, Q., & Wang, J. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0908 · Cited by 34 · see citing works
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Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133 · see citing works
Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113 · see citing works
Morris, M., Maeda, S., Vossel, K., & Mucke, L. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.009 · Cited by 899 · see citing works
Therapeutics of Alzheimer's disease: Past, present and future
Anand, R., Gill, K. D., & Mahdi, A. A. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.07.004 · Cited by 748 · see citing works
Yanamandra, 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
DeVos, S. L., Miller, R. L., Schoch, K. M., Holmes, B. B., Kebodeaux, C. S., Wegener, A. J., Chen, G., Shen, T., Tran, H., Nichols, B., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aag0481 · Cited by 516 · see citing works
Inflammatory process in Alzheimer's Disease
Meraz-Ríos, M. A., Toral-Rios, D., Franco-Bocanegra, D., Villeda-Hernández, J., & Campos-Peña, V. (2013) · Frontiers in Integrative Neuroscience · doi:10.3389/fnint.2013.00059 · Cited by 427 · see citing works
Review on Alzheimer’s Disease: Inhibition of Amyloid Beta and Tau Tangle Formation
Ashrafian, H., Zadeh, E. H., & Khan, R. H. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.11.192 · Cited by 368 · see citing works
Passive 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 346 · 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
A 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
Synaptic Tau Seeding Precedes Tau Pathology in Human Alzheimer’s Disease Brain
DeVos, S. L., Corjuc, B. T., Oakley, D. H., Nobuhara, C. K., Bannon, R. N., Chase, A., Commins, C., Gonzalez, J. A., Dooley, P. M., Frosch, M. P., et al. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00267 · Cited by 285 · see citing works
Castillo-Carranza, D. L., Sengupta, U., Guerrero-Muñoz, M. J., Lasagna-Reeves, C. A., Gerson, J. E., Singh, G., Estes, D. M., Barrett, A. D. T., Dineley, K. T., Jackson, G. R., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.3192-13.2014 · Cited by 278 · see citing works
“Active vaccination using phosphorylated tau fragments (Asuni et al., 2007; Boimel et al., 2010; Bi et al., 2011), and passive vaccination using antibodies directed against NFT-associated tau phosphoepitopes (Boutajangout et al., 2011; Chai et al., 2011; Gu and Sigurdsson, 2011) have been reported…”
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Tau-based therapies in neurodegeneration: opportunities and challenges
Li, C., & Götz, J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.155 · Cited by 272 · see citing works
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Härd, T., & Lendel, C. (2012) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.12.062 · Cited by 266 · 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
“Several preclinical studies of immunotherapy targeting protein Tau have now been published [55–62].”
BackgroundNakamura, K., Greenwood, A., Binder, L. I., Bigio, E. H., Denial, S., Nicholson, L. K., Zhou, X. Z., & Lu, K. P. (2012) · Cell · doi:10.1016/j.cell.2012.02.016 · Cited by 255 · see citing works
Protein phosphorylation in neurodegeneration: friend or foe?
Tenreiro, S., Eckermann, K., & Outeiro, T. F. (2014) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2014.00042 · Cited by 252 · see citing works
Kontseková, E., Žilka, N., Kováčech, B., Novák, P., & Novák, M. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt278 · Cited by 248 · see citing works
Tau 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
Luo, W., Liu, W., Hu, X., Hanna, M., Caravaca, A., & Paul, S. M. (2015) · Scientific Reports · doi:10.1038/srep11161 · Cited by 241 · see citing works
Developing Therapeutic Antibodies for Neurodegenerative Disease
Yu, Y. J., & Watts, R. J. (2013) · Neurotherapeutics · doi:10.1007/s13311-013-0187-4 · Cited by 227 · see citing works
Constitutive secretion of tau protein by an unconventional mechanism
Chai, X., Dage, J. L., & Citron, M. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.05.021 · Cited by 224 · see citing works
Tau in neurodegenerative disease
Gao, Y.-L., Wang, N., Sun, F.-R., Cao, X.-P., Zhang, W., & Yu, J.-T. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.04.23 · Cited by 222 · see citing works
Intersection of pathological tau and microglia at the synapse
Vogels, T., Murgoci, A.-N., & Hromádka, T. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0754-y · Cited by 197 · see citing works
Congdon, E. E., Gu, J., Sait, H. B. R., & Sigurdsson, E. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.491001 · Cited by 195 · see citing works
Zommer, N., Sergeant, N., Schraen-Maschke, S., Blum, D., & Buee, L. (2012) · Current Alzheimer Research · doi:10.2174/156720512800492503 · Cited by 193 · see citing works
Tau passive immunization inhibits not only tau but also Aβ pathology
Dai, C., Tung, Y. C., Liu, F., Gong, C., & Iqbal, K. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-016-0227-5 · Cited by 186 · see citing works
Anti‐tau antibody reduces insoluble tau and decreases brain atrophy
Yanamandra, K., Jiang, H., Mahan, T. E., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.176 · Cited by 185 · see citing works
Exploiting microglial and peripheral immune cell crosstalk to treat Alzheimer’s disease
Dionisio-Santos, D. A., Olschowka, J. A., & O’Banion, M. K. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1453-0 · Cited by 184 · see citing works
Kitazawa, M., Medeiros, R., & M. LaFerla, F. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212799315786 · Cited by 178 · see citing works
Protein aggregation and neurodegenerative diseases: From theory to therapy
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Tau Biology and Tau-Directed Therapies for Alzheimer’s Disease
Bakota, L., & Brandt, R. (2016) · Drugs · doi:10.1007/s40265-015-0529-0 · Cited by 170 · see citing works
Gu, J., Congdon, E. E., & Sigurdsson, E. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.494922 · Cited by 163 · see citing works
Tissue-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 154 · see citing works
Bi, M., Ittner, A., Ke, Y. D., Götz, J., & Ittner, L. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026860 · Cited by 153 · see citing works
Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Sengupta, U., Hernandez, C., Barrett, A. D. T., Dineley, K., & Kayed, R. (2015) · The Journal of Neuroscience · doi:10.1523/jneurosci.4989-14.2015 · Cited by 149 · see citing works
Sankaranarayanan, S., Barten, D. M., Vana, L., Devidze, N., Yang, L., Cadelina, G. W., Hoque, N., DeCarr, L. B., Keenan, S., Lin, A., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125614 · Cited by 143 · see citing works
Therapeutic strategies for tau mediated neurodegeneration
Yoshiyama, Y., Lee, V. M. ‐., & Trojanowski, J. Q. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-303144 · Cited by 129 · see citing works
“Prion‐Like” Templated Misfolding in Tauopathies
Clavaguera, F., Lavenir, I., Falcon, B., Frank, S., Goedert, M., & Tolnay, M. (2013) · Brain Pathology · doi:10.1111/bpa.12044 · Cited by 129 · see citing works
Tau‐targeted treatment strategies in Alzheimer's disease
Götz, J., Ittner, A., & Ittner, L. M. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01713.x · Cited by 127 · see citing works
Alajangi, H. K., Kaur, M., Sharma, A., Rana, S., Thakur, S., Chatterjee, M., Singla, N., Jaiswal, P. K., Singh, G., & Barnwal, R. P. (2022) · Molecular Brain · doi:10.1186/s13041-022-00937-4 · Cited by 130 · see citing works
Immunotherapy for Alzheimer‘s Disease: From Anti-β-Amyloid to Tau-Based Immunization Strategies
Panza, F., Frisardi, V., Solfrizzi, V., Imbimbo, B. P., Logroscino, G., Santamato, A., Greco, A., Seripa, D., & Pilotto, A. (2012) · Immunotherapy · doi:10.2217/imt.11.170 · Cited by 125 · see citing works
Nobuhara, C. K., DeVos, S. L., Commins, C., Wegmann, S., Moore, B. D., Roe, A. D., Costantino, I., Frosch, M. P., Pitstick, R., Carlson, G. A., et al. (2017) · The American Journal of Pathology · doi:10.1016/j.ajpath.2017.01.022 · Cited by 120 · see citing works
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Cárdenas-Aguayo, M. D. C., Gómez-Virgilio, L., DeRosa, S., & Meraz-Ríos, M. A. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500148z · Cited by 120 · see citing works
New perspectives on the role of tau in Alzheimer's disease. Implications for therapy
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Progress and Developments in Tau Aggregation Inhibitors for Alzheimer Disease
Bulic, B., Pickhardt, M., & Mandelkow�, E. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm3017317 · Cited by 116 · see citing works
Tau as a therapeutic target in neurodegenerative disease
Himmelstein, D. S., Ward, S., Lancia, J. K., Patterson, K. R., & Binder, L. I. (2012) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.07.001 · Cited by 113 · see citing works
Kontsekova, E., Zilka, N., Kovacech, B., Skrabana, R., & Novak, M. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt277 · Cited by 112 · see citing works
Therapeutic strategies for the treatment of tauopathies: Hopes and challenges
Khanna, M. R., Kovalevich, J., Lee, V. M. ‐., Trojanowski, J. Q., & Brunden, K. R. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.06.006 · Cited by 112 · see citing works
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Ando, K., Maruko-Otake, A., Ohtake, Y., Hayashishita, M., Sekiya, M., & Iijima, K. M. (2016) · PLOS Genetics · doi:10.1371/journal.pgen.1005917 · Cited by 105 · see citing works
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Boutajangout, A., & Wısnıewskı, T. (2014) · Gerontology · doi:10.1159/000358875 · Cited by 105 · see citing works
Yang, H., Sun, Z., & Chen, S. (2012) · Translational Neurodegeneration · doi:10.1186/2047-9158-1-21 · Cited by 102 · see citing works
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Ong, W.-Y., Tanaka, K., Dawe, G. S., Ittner, L. M., & Farooqui, A. A. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-121990 · Cited by 101 · see citing works
Panza, F., Solfrizzi, V., Imbimbo, B. P., Tortelli, R., Santamato, A., & Logroscino, G. (2014) · Expert Review of Clinical Immunology · doi:10.1586/1744666x.2014.883921 · Cited by 97 · see citing works
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Winblad, B. G., Graf, A., Riviere, M., Andreasen, N., & Ryan, J. M. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt237 · Cited by 100 · see citing works
The Role of Tau in Neurodegenerative Diseases and Its Potential as a Therapeutic Target
Wolfe, M. S. (2012) · Scientifica · doi:10.6064/2012/796024 · Cited by 97 · see citing works
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Zhang, C., Xing, A., Tan, M., Tan, L., & Yu, J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9415-8 · Cited by 91 · see citing works
Dai, C., Chen, X., Kazim, S. F., Liu, F., Gong, C., Grundke, I., & Iqbal, K. (2014) · Journal of Neural Transmission · doi:10.1007/s00702-014-1315-y · Cited by 90 · see citing works
The toxicity of tau in Alzheimer disease: turnover, targets and potential therapeutics
Pritchard, S. M., Dolan, P. J., Vitkus, A., & Johnson, G. V. W. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01273.x · Cited by 89 · see citing works
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Lourbopoulos, A. I., Ertürk, A., & Hellal, F. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00054 · Cited by 89 · see citing works
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Chiang, K., & Koo, E. H. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-135932 · Cited by 88 · see citing works
Sigurdsson, E. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179937 · Cited by 76 · see citing works
Wang, H., Wang, R., Carrera, I., Xu, S., & Lakshmana, M. K. (2016) · eNeuro · doi:10.1523/eneuro.0042-16.2016 · Cited by 76 · see citing works
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Gerson, J. E., Castillo‐Carranza, D. L., & Kayed, R. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500143n · Cited by 73 · see citing works
Krishnamurthy, P., Deng, Y., & Sigurdsson, E. M. (2011) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00059 · Cited by 71 · see citing works
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Ittner, L. M., Halliday, G. M., Kril, J. J., Götz, J., Hodges, J. R., & Kiernan, M. C. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.65 · Cited by 69 · see citing works
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Sigurdsson, E. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-189010 · Cited by 67 · see citing works
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Rozenstein-Tsalkovich, L., Grigoriadis, N., Lourbopoulos, A., Nousiopoulou, E., Kassis, I., Abramsky, O., Karussis, D., & Rosenmann, H. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.07.006 · Cited by 66 · see citing works
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Krishnaswamy, S., Lin, Y., Rajamohamedsait, W. J., Rajamohamedsait, H. B., Krishnamurthy, P., & Sigurdsson, E. M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2755-14.2014 · Cited by 62 · see citing works
Agadjanyan, M. G., Petrovsky, N., & Ghochikyan, A. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.06.1884 · Cited by 65 · see citing works
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Zhou, Q., Mareljic, N., Michaelsen, M., Parhizkar, S., Heindl, S., Nuscher, B., Farny, D., Czuppa, M., Schludi, C., Graf, A., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201910919 · Cited by 62 · see citing works
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Oakley, S. S., Maina, M. B., Marshall, K. E., Al‐Hilaly, Y. K., Harrington, C., Wischik, C. M., & Serpell, L. C. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.590754 · Cited by 57 · see citing works
Clavaguera, F., Grueninger, F., & Tolnay, M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.08.037 · Cited by 60 · see citing works
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Acker, C. M., Forest, S. K., Zinkowski, R., Davies, P., & d’Abramo, C. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.05.010 · Cited by 58 · see citing works
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Huang, Y., Wu, Z., & Zhou, B. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2042-8 · Cited by 58 · see citing works
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Walls, K. C., Ager, R. R., Vasilevko, V., Cheng, D., Medeiros, R., & LaFerla, F. M. (2014) · Neuroscience Letters · doi:10.1016/j.neulet.2014.05.047 · Cited by 58 · see citing works
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Pul, R., Dodel, R. C., & Stangel, M. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.552884 · Cited by 58 · see citing works
Bartoš, A., Fialová, L., Švarcová, J., & Řı́pová, D. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.08.001 · Cited by 57 · see citing works
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Agadjanyan, M. G., Zagorski, K., Petrushina, I., Davtyan, H., Kazarian, K., Antonenko, M., Davis, J. L., Bon, C., Blurton-Jones, M. M., Cribbs, D. H., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0172-1 · Cited by 53 · see citing works
Strang, K. H., Goodwin, M. S., Riffe, C. J., Moore, B. D., Chakrabarty, P., Levites, Y., Golde, T. E., & Giasson, B. I. (2017) · Acta Neuropathologica Communications · doi:10.1186/s40478-017-0458-0 · Cited by 52 · see citing works
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Rajamohamedsait, H., Rasool, S., Rajamohamedsait, W., Lin, Y., & Sigurdsson, E. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-17313-1 · Cited by 49 · see citing works
Schroeder, S. K., Joly‐Amado, A., Gordon, M. N., & Morgan, D. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9637-6 · Cited by 49 · see citing works
The P2X7 receptor: a new therapeutic target in Alzheimer’s disease
Illés, P., Rubini, P., Huang, L., & Tang, Y. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1575811 · Cited by 49 · see citing works
Katsinelos, T., Tuck, B. J., Mukadam, A. S., & McEwan, W. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01139 · Cited by 44 · see citing works
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Noble, W. J., Pooler, A. M., & Hanger, D. P. (2011) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2011.586690 · Cited by 44 · see citing works
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Braczynski, A. K., Schulz, J. B., & Bach, J. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14207 · Cited by 43 · see citing works
Further understanding of tau phosphorylation: implications for therapy
Medina, M., & Avila, J. (2015) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2015.1000864 · Cited by 41 · see citing works
Selenica, M.-L. B., Davtyan, H., Housley, S. B., Blair, L. J., Gillies, A., Nordhues, B. A., Zhang, B., Liu, J., Gestwicki, J. E., Lee, D. C., et al. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0152-0 · Cited by 40 · see citing works
Invited review: Drug development for tauopathies
Grüninger, F. (2014) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12192 · Cited by 40 · see citing works
Panza, F., Frisardi, V., Imbimbo, B. P., Seripa, D., Solfrizzi, V., & Pilotto, A. (2011) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.2011.579099 · Cited by 38 · see citing works
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Coughlin, D. G., & Irwin, D. J. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0779-1 · Cited by 39 · see citing works
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Lambracht‐Washington, D., & Rosenberg, R. N. (2013) · ImmunoTargets and Therapy · doi:10.2147/itt.s31428 · Cited by 38 · see citing works
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Lahiani-Cohen, I., Lourbopoulos, A. I., Haber, E., Rozenstein‐Tsalkovich, L., Abramsky, O., Grigoriadis, N., & Rosenmann, H. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318221bfab · Cited by 37 · see citing works
Self-citation
- Authors
- Boimel, M., Grigoriadis, N., Lourbopoulos, A., Haber, E., Abramsky, O., & Rosenmann, H.
- Affiliations
- Hebrew University of Jerusalem (IL)
- AHEPA University Hospital (GR)
- Corresponding author
- Rosenmann, Hanna
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2010-08
- Volume
- 224
- Issue
- 2
- Pages
- 472-485
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2091935655
- Cited by
- 174
- References
- 41
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 4 · 2020: 8 · 2019: 10 · 2018: 11 · 2017: 15 · 2016: 8 · 2015: 19 · 2014: 32 · 2013: 23 · 2012: 15
- FWCI
- 12.56
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-09-01)
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- phosphorylated tau, neurofibrillary tangles, tau immunotherapy, Alzheimer's disease, tauopathy, encephalitogenicity, microglia, lysosomal proteases, anti-tau antibodies, pertussis toxin, complete Freund's adjuvant, neuroinflammation
- MeSH terms
- Animals, Antibodies, Astrocytes, Brain, Cathepsin D, Encephalitis, Female, Immunization, Lysosomes, Mice, Transgenic, Neurons, Peptide Fragments, Peptide Hydrolases, Phosphoproteins, Vaccines, Synthetic, Neurofibrillary Tangles, tau Proteins, Microglia, Tauopathies, Mice, Cathepsin L
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