AAV-mediated expression of anti-tau scFvs decreases tau accumulation in a mouse model of tauopathy
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Tauopathies are characterized by the progressive accumulation of hyperphosphorylated, aggregated forms of tau. Our laboratory has previously demonstrated that passive immunization with an anti-tau antibody, HJ8.5, decreased accumulation of pathological tau in a human P301S tau-expressing transgenic (P301S-tg) mouse model of frontotemporal dementia/tauopathy. To investigate whether the Fc domain of HJ8.5 is required for the therapeutic effect, we engineered single-chain variable fragments (scFvs) derived from HJ8.5 with variable linker lengths, all specific to human tau. Based on different binding properties, we selected two anti-tau scFvs and tested their efficacy in vivo by adeno-associated virus–mediated gene transfer to the brain of P301S-tg mice. The scFvs significantly reduced levels of hyperphosphorylated, aggregated tau in brain tissue of P301S-tg mice, associated with a decrease in detergent-soluble tau species. Interestingly, these mice showed substantial levels of scFvs in the cerebrospinal fluid without significant effects on total extracellular tau levels. Therefore, our study provides a novel strategy for anti-tau immunotherapeutics that potentially limits a detrimental proinflammatory response.
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Antibody fragments have been shown to reduce tau levels in vivo.
“Moreover, antibody fragments have been shown to reduce tau levels in vivo225,226.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [226]
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A protein factor essential for microtubule assembly
Weingarten, M. D., Lockwood, A. H., Hwo, S. Y., & Kirschner, M. W. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.5.1858 · Cited by 3,089 · see citing works
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · see citing works
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480 · see citing works
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., et al. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31825018f7 · Cited by 2,050 · cited 1× · see citing works
“Interestingly, evidence suggests that accumulation of tau correlates with brain atrophy and clinical symptoms in Alzheimer’s disease patients and other tauopathies (Nelson et al., 2012; Brier et al., 2016; Johnson et al., 2016).”
BackgroundDepletion 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
Propagation of Tau Pathology in a Model of Early Alzheimer's Disease
de Calignon, A., Polydoro, M., Suárez-Calvet, M., William, C., Adamowicz, D. H., Kopeikina, K. J., Pitstick, R., Sahara, N., Ashe, K. H., Carlson, G. A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.033 · Cited by 1,427 · 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
Tau positron emission tomographic imaging in aging and early <scp>A</scp> lzheimer disease
Johnson, K. A., Schultz, A., Betensky, R. A., Becker, J. A., Sepulcre, J., Rentz, D., Mormino, E., Chhatwal, J., Amariglio, R., Papp, K., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24546 · Cited by 986 · see citing works
Goedert, M., & Jakes, R. (1990) · The EMBO Journal · doi:10.1002/j.1460-2075.1990.tb07870.x · Cited by 929 · cited 1× · see citing works
“Recombinant htau Recombinant human P301S (1N4R) and WT tau (2N4R) were cloned into pRK172 and purified as described previously (Goedert and Jakes, 1990).”
MethodscFv Antibody: Principles and Clinical Application
Ahmad, Z. A., Yeap, S. K., Ali, A. M., Ho, W. Y., Alitheen, N. B., & Hamid, M. (2012) · Clinical and Developmental Immunology · doi:10.1155/2012/980250 · Cited by 761 · see citing works
Tau and Aβ imaging, CSF measures, and cognition in Alzheimer’s disease
Brier, M. R., Gordon, B., Friedrichsen, K., McCarthy, J., Stern, A., Christensen, J., Owen, C., Aldea, P., Su, Y., Hassenstab, J., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf2362 · Cited by 734 · see citing works
Self-citationProteopathic 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 · see citing works
Self-citationCulturing pyramidal neurons from the early postnatal mouse hippocampus and cortex
Beaudoin, G. M. J., Lee, S.-H., Singh, D., Yuan, Y., Ng, Y., Reichardt, L. F., & Arikkath, J. (2012) · Nature Protocols · doi:10.1038/nprot.2012.099 · Cited by 655 · 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
Self-citationNeuronal activity regulates extracellular tau in vivo
Yamada, K., Holth, J. K., Liao, F., Stewart, F. R., Mahan, T. E., Jiang, H., Cirrito, J. R., Patel, T. K., Hochgräfe, K., Mandelkow, E., et al. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131685 · Cited by 574 · see citing works
Self-citationAlzheimer brain-derived tau oligomers propagate pathology from endogenous tau
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., & Kayed, R. (2012) · Scientific Reports · doi:10.1038/srep00700 · Cited by 502 · see citing works
Ahmed, Z., Cooper, J., Murray, T. K., Garn, K., McNaughton, E., Clarke, H., Parhizkar, S., Ward, M. A., Cavallini, A., Jackson, S., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1254-6 · Cited by 460 · see citing works
Zhang, B., Carroll, J., Trojanowski, J. Q., Yao, Y., Iba, M., Potuzak, J. S., Hogan, A.-M. L., Xie, S. X., Ballatore, C., Smith, A. B., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.4922-11.2012 · Cited by 401 · 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
Adolfsson, O., Pihlgren, M., Toni, N., Varisco, Y., Buccarello, A. L., Antoniello, K., Lohmann, S., Piorkowska, K., Gafner, V., Atwal, J. K., et al. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4742-11.2012 · Cited by 317 · 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
Jeganathan, S., von Bergen, M., Mandelkow, E.-M., & Mandelkow, E. (2008) · Biochemistry · doi:10.1021/bi800783d · Cited by 286 · see citing works
Demattos, R. B., Bales, K. R., Parsadanian, M., O'Dell, M. A., Foss, E. M., Paul, S. M., & Holtzman, D. M. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00889.x · Cited by 253 · see citing works
Self-citationTubulin requires tau for growth onto microtubule initiating sites.
Witman, G. B., Cleveland, D. W., Weingarten, M. D., & Kirschner, M. W. (1976) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.73.11.4070 · Cited by 238 · see citing works
Capsid Serotype and Timing of Injection Determines AAV Transduction in the Neonatal Mice Brain
Chakrabarty, P., Rosario, A. M., Cruz, P. E., Siemienski, Z. B., Ceballos‐Diaz, C., Crosby, K. W., Jansen, K. R., Borchelt, D., Kim, J., Jankowsky, J. L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067680 · Cited by 201 · 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
Self-citationInvited review: Prion‐like transmission and spreading of tau pathology
Clavaguera, F., Hench, J., Goedert, M., & Tolnay, M. (2015) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12197 · Cited by 156 · 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
Tau Passive Immunotherapy in Mutant P301L Mice: Antibody Affinity versus Specificity
d’Abramo, C., Acker, C. M., Jimenez, H. T., & Davies, P. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062402 · Cited by 144 · 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
Lee, S.-H., Le Pichon, C. E., Adolfsson, O., Gafner, V., Pihlgren, M., Lin, H., Solanoy, H., Brendza, R., Ngu, H., Foreman, O., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.099 · Cited by 125 · see citing works
Multimerization behaviour of single chain Fv variants for the tumour-binding antibody B72.3
Desplancq, D., King, D. J., Lawson, A. D. G., & Mountain, A. (1994) · Protein Engineering Design and Selection · doi:10.1093/protein/7.8.1027 · Cited by 123 · see citing works
Dosing in phase II trial of Alzheimer's vaccine suspended
Senior, K. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00023-6 · Cited by 88 · see citing works
Clinical Applications Involving CNS Gene Transfer
Kantor, B., McCown, T., Leone, P., & Gray, S. J. (2014) · Advances in Genetics · doi:10.1016/b978-0-12-800149-3.00002-0 · Cited by 74 · see citing works
Single-Chain Fragment Variable Passive Immunotherapies for Neurodegenerative Diseases
Huang, L., Su, L., & Federoff, H. J. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140919109 · Cited by 47 · see citing works
Freeman, G. B., Brown, T. P., Wallace, K., & Bales, K. R. (2012) · Current Alzheimer Research · doi:10.2174/156720512803569064 · Cited by 20 · see citing works
Sheikholvaezin, A., Sandström, P., Eriksson, D., Norgren, N., Riklund, K., & Stigbrand, T. I. (2006) · Hybridoma · doi:10.1089/hyb.2006.25.181 · Cited by 17 · see citing works
Flagged first, then by citations
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Sorted by citations
NLRP3 inflammasome activation drives tau pathology
Ising, C., Venegas, C., Zhang, S., Scheiblich, H., Schmidt, S. V., Vieira-Saecker, A., Schwartz, S., Albasset, S., McManus, R. M., Tejera, D., et al. (2019) · Nature · doi:10.1038/s41586-019-1769-z · Cited by 1,487 · see citing works
Self-citationTau-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
Leyns, C. E. G., Ulrich, J. D., Finn, M. B., Stewart, F. R., Koscal, L. J., Remolina Serrano, J., Robinson, G. O., Anderson, E., Colonna, M., & Holtzman, D. M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1710311114 · Cited by 517 · see citing works
“quantified in a tau sandwich ELISA as previously described (48) using Tau-5 as”
MethodInfluentialSelf-citationTau-targeting therapies for Alzheimer disease: Current status and future directions
Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00883-2 · Cited by 371 · see citing works
Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.110 · Cited by 306 · see citing works
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
Erratum: Gene therapy for neurological disorders: progress and prospects
Deverman, B. E., Ravina, B. M., Bankiewicz, K. S., Paul, S. M., & Sah, D. W. Y. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.158 · Cited by 248 · 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
From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy
Colin, M., Dujardin, S., Schraen-Maschke, S., Meno-Tetang, G., Duyckaerts, C., Courade, J.-P., & Buée, L. (2020) · Acta Neuropathologica · doi:10.1007/s00401-019-02087-9 · Cited by 187 · see citing works
Höglinger, G. U., Litvan, I., Mendonça, N., Wang, D., Zheng, H., Rendenbach‐Mueller, B., Lon, H., Jin, Z., Fisseha, N., Budur, K. S., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30489-0 · Cited by 146 · see citing works
Disease-Modifying Therapies for Alzheimer’s Disease: More Questions than Answers
Golde, T. E. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01201-2 · Cited by 119 · see citing works
Li, H., Liu, C.-C., Zheng, H., & Huang, T. Y. (2018) · Translational Neurodegeneration · doi:10.1186/s40035-018-0139-3 · Cited by 103 · see citing works
Current Status of Clinical Trials on Tau Immunotherapies
Ji, C., & Sigurdsson, E. M. (2021) · Drugs · doi:10.1007/s40265-021-01546-6 · Cited by 96 · see citing works
Tau immunotherapies: Lessons learned, current status and future considerations
Sandusky-Beltran, L. A., & Sigurdsson, E. M. (2020) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108104 · Cited by 90 · see citing works
Sigurdsson, E. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179937 · Cited by 76 · see citing works
Mann, C. N., Devi, S. S., Kersting, C. T., Bleem, A. V., Karch, C. M. M., Holtzman, D. M., & Gallardo, G. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abm4107 · Cited by 73 · see citing works
Self-citationTau Immunotherapies for Alzheimer’s Disease and Related Tauopathies: Progress and Potential Pitfalls
Sigurdsson, E. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-189010 · Cited by 67 · see citing works
Kumar, N. N., Pizzo, M. E., Nehra, G., Wilken-Resman, B., Boroumand, S., & Thorne, R. G. (2018) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.8b00548 · Cited by 57 · see citing works
Targeting Alzheimer's disease with gene and cell therapies
Loera‐Valencia, R., Piras, A., Ismail, M.-A.-M., Manchanda, S., Eyjolfsdottir, H., Saido, T. C., Johansson, J., Eriksdotter, M., Winblad, B. G., & Nilsson, P. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12759 · Cited by 57 · see citing works
Vitale, F., Giliberto, L., Ruiz, S., Steslow, K., Marambaud, P., & d’Abramo, C. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0585-2 · Cited by 54 · see citing works
Targeting tauopathy with engineered tau-degrading intrabodies
Gallardo, G., Wong, C. H. Y., Hernandez, S. M. R., Mann, C. N., Lin, K., Leyns, C. E. G., Jiang, H., & Holtzman, D. M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0340-6 · Cited by 55 · see citing works
Self-citationNisbet, R. M., & Götz, J. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179907 · Cited by 55 · see citing works
Goodwin, M. S., Sinyavskaya, O., Burg, F., O’Neal, V., Ceballos‐Diaz, C., Cruz, P. E., Lewis, J. M., Giasson, B. I., Davies, P., Golde, T. E., et al. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.10.007 · Cited by 42 · see citing works
Regional vulnerability and spreading of hyperphosphorylated tau in seeded mouse brain
Detrez, J. R., Maurin, H., Van Kolen, K., Willems, R., Colombelli, J., Lechat, B., Roucourt, B., Van Leuven, F., Baatout, S., Larsen, P., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.03.010 · Cited by 39 · see citing works
Dupré, E., Danis, C., Arrial, A., Hanoulle, X., Homa, M., Cantrelle, F., Merzougui, H., Colin, M., Rain, J., Buée, L., et al. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00217 · Cited by 35 · see citing works
Adeno‐associated virus‐based Alzheimer's disease mouse models and potential new therapeutic avenues
Ittner, L. M., Klugmann, M., & Ke, Y. D. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14637 · Cited by 35 · see citing works
Spencer, B. J., Brüschweiler, S., Sealey‐Cardona, M., Rockenstein, E. M., Adame, A., Florio, J. B., Mante, M., Trinh, I., Rissman, R. A., Konrat, R., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1869-0 · Cited by 28 · see citing works
Neuro-Immuno-Gene- and Genome-Editing-Therapy for Alzheimer’s Disease: Are We There Yet?
Raikwar, S. P., Thangavel, R., Dubova, I., Ahmed, M. E., Selvakumar, G. P., Kempuraj, D., Zaheer, S. A., Iyer, S. S., & Zaheer, A. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180422 · Cited by 26 · see citing works
Neuronally expressed anti-tau scFv prevents tauopathy-induced phenotypes in Drosophila models
Krishnaswamy, S., Huang, H.-W., Marchal, I. S., Ryoo, H. D., & Sigurdsson, E. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104770 · Cited by 23 · see citing works
miR-188 promotes liver steatosis and insulin resistance via the autophagy pathway
Liu, Y., Zhou, X., Xiao, Y., Li, C., Huang, Y., Guo, Q., Su, T., Fu, L., & Luo, L. (2020) · Journal of Endocrinology · doi:10.1530/joe-20-0033 · Cited by 25 · see citing works
Ng, P. Y., Chang, I. S., Koh, R. Y., & Chye, S. M. (2020) · Metabolic Brain Disease · doi:10.1007/s11011-020-00591-6 · Cited by 24 · see citing works
AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System
Marino, M., & Holt, M. G. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.870799 · Cited by 24 · see citing works
Directed evolution of a picomolar-affinity, high-specificity antibody targeting phosphorylated tau
Li, D., Wang, L., Maziuk, B. F., Yao, X., Wolozin, B. L., & Cho, Y. K. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.003557 · Cited by 20 · see citing works
Genetic Therapies for Alzheimer’s Disease: A Scoping Review
Lennon, M. J., Rigney, G., Raymont, V., & Sachdev, P. S. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-215145 · Cited by 20 · see citing works
Messenger RNA-encoded antibody approach for targeting extracellular and intracellular tau
Wongsodirdjo, P., Caruso, A. C., Yong, A., Lester, M. A., Vella, L. J., Hung, Y. H., & Nisbet, R. M. (2024) · Brain Communications · doi:10.1093/braincomms/fcae100 · Cited by 20 · see citing works
New insights into the therapeutic approaches for the treatment of tauopathies
Singh, H., Das, A., Khan, M. M., & Pourmotabbed, T. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385288 · Cited by 18 · see citing works
Design, Synthesis, and Bioactivity of Novel Bifunctional Small Molecules for Alzheimer’s disease
Liang, M., Gu, L., Zhang, H., Min, J., Wang, Z., Ma, Z., Zhang, C., Zeng, S., Pan, Y., Yan, D., et al. (2022) · ACS Omega · doi:10.1021/acsomega.2c02130 · Cited by 17 · see citing works
Bitencourt, A. L. B., de Campos, R. M., Cline, E. N., Klein, W. L., & Sebollela, A. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21238920 · Cited by 16 · see citing works
Proteostasis as a fundamental principle of Tau immunotherapy
Cruz, E., Nisbet, R. M., Padmanabhan, P., Waardenberg, A. J., Graham, M. E., Nkajja, G., Tapaswi, S., Connor, B. J., Robinson, P., & Götz, J. (2024) · Brain · doi:10.1093/brain/awae254 · Cited by 14 · see citing works
Zhuang, J., Wang, S., Shan, Q., Zhang, Z.-F., Li, M., Zheng, G., Fan, S., Wu, D., Hu, B., Lu, J. L., et al. (2018) · Journal of Hazardous Materials · doi:10.1016/j.jhazmat.2018.01.008 · Cited by 10 · see citing works
Duechs, M. J., Blazevic, D., Rechtsteiner, P., Kenny, C. H., Lamla, T., Low, S. H. H., Savistchenko, J., Neumann, M., Melki, R., Schönberger, T., et al. (2023) · npj Parkinson s Disease · doi:10.1038/s41531-023-00542-9 · Cited by 9 · see citing works
Li, S., Yi, Y., Cui, K., Zhang, Y., Chen, Y., Han, D., Sun, L. V., Zhang, X., Chen, F., Zhang, Y., et al. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-191266 · Cited by 8 · see citing works
Zhang, Y., Yu, W., Zhang, L., & Li, P. (2024) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2024.2396911 · Cited by 6 · see citing works
Min, L., Fang, L., Wang, X., Chen, X., Liu, L., Zhang, H., & Dong, K. (2020) · Cancer Cell International · doi:10.1186/s12935-020-1159-5 · Cited by 5 · see citing works
Recent Advances and Future Directions in Alzheimer’s Disease Genetic Research
Stancheva, M., Toncheva, D. I., & Karachanak-Yankova, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26167819 · Cited by 4 · see citing works
Tau Pathology in Neurodegenerative Diseases
Vogels, T., & Hromádka, T. (2021) · Neuromethods · doi:10.1007/978-1-0716-1712-0_4 · Cited by 2 · see citing works
Anti-tau VHH therapy against PHF6: a safe approach to slowing the phenotype of tau pathology
Caillierez, R., Leboullenger, C., Leclercq, S., Besegher, M., Bégard, S., Auger, F., Maurage, C., Accart, B., Mortelecque, J., Dupré, E., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01823-6 · Cited by 1 · see citing works
Jiang, Y., Tetlow, A. M., Lin, Y., Ji, C., Ader, J., Laborc, K. F., Mar, A. C., Pan, R., Kong, X., Congdon, E. E., et al. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.aea4205 · Cited by 2 · see citing works
Alzheimer’s Disease and Frontotemporal Lobar Degeneration: Mouse Models
Ittner, L. M., Lee, W. S., Stefanoska, K., Asih, P. R., & Ke, Y. D. (2018) · Springer eBooks · doi:10.1007/978-3-319-72938-1_10 · Cited by 1 · see citing works
Jiang, Y., Tetlow, A. M., Lin, Y., Ji, C., Laborc, K. F., Mar, A. C., Pan, R., Kong, X., Congdon, E. E., & Sigurdsson, E. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.30.662446 · Cited by 1 · see citing works
Faculty Opinions recommendation of NLRP3 inflammasome activation drives tau pathology.
Skolnick, J. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.736936731.793568907
Duechs, M. J., Blazevic, D., Rechtsteiner, P., Kenny, C. H., Lamla, T., Low, S. H. H., Savistchenko, J., Neumann, M., Melki, R., Schönberger, T., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.11.30.518485
Wongsodirdjo, P., Caruso, A. C., Yong, A., Lester, M. A., Vella, L. J., Hung, Y. H., & Nisbet, R. M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.15.563554
Caruso, A. C., Kavanagh, T., Waardenberg, A. J., Graham, M. E., Drummond, E., & Nisbet, R. M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.13.665777
Kertser, A., Baruch, K., & Schwartz, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.28.679024
Yu, Z., Li, Y., Zhang, Z., & Yin, R. (2026) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2026.1901875
- Authors
- Ising, C., Gallardo, G., Leyns, C. E. G., Wong, C. H., Jiang, H., Stewart, F., Koscal, L. J., Roh, J., Robinson, G. O., Remolina Serrano, J., & Holtzman, D. M.
- Affiliations
- Washington University in St. Louis (US)
- Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer's Disease Research Center, Washington University, St. Louis, MO 63110
- Corresponding author
- Holtzman, David M.
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2017-04-17
- Volume
- 214
- Issue
- 5
- Pages
- 1227-1238
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC5413341
- OpenAlex
- W2607091076
- Cited by
- 57
- References
- 39
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 8 · 2018: 16 · 2017: 2
- FWCI
- 6.67
- Type
- journal article
- Language
- en
- Update notices
- correction (2017-05-23)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-sa)
- Funders
- Deutsche Forschungsgemeinschaft (IS 299/1-1)
- National Institutes of Health (K01 NS096719-01)
- McDonnell Center for Cellular and Molecular Neurobiology
- NIH (AG04867801, S10 RR027552)
- Tau Consortium
- JPB Foundation
- C2N Diagnostics
- The Hope Center
- Washington University
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- tauopathy, scFv, AAV gene delivery, P301S tau transgenic mice, frontotemporal dementia, hyperphosphorylated tau, tau aggregation, passive immunization, cerebrospinal fluid, Fc domain
- MeSH terms
- Dependovirus, Animals, Brain, Disease Models, Animal, Female, Hippocampus, Male, Mice, Transgenic, tau Proteins, Gene Transfer Techniques, Tauopathies, Mice, Single-Chain Antibodies
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