Human secreted tau increases amyloid-beta production
Open accessAbstract
The interaction of amyloid-beta (Aβ) and tau in the pathogenesis of Alzheimer's disease is a subject of intense inquiry, with the bulk of evidence indicating that changes in tau are downstream of Aβ. It has been shown however, that human tau overexpression in amyloid precursor protein transgenic mice increases Aβ plaque deposition. Here, we confirm that human tau increases Aβ levels. To determine if the observed changes in Aβ levels were because of intracellular or extracellular secreted tau (eTau for extracellular tau), we affinity purified secreted tau from Alzheimer's disease patient-derived cortical neuron conditioned media and analyzed it by liquid chromatography-mass spectrometry. We found the extracellular species to be composed predominantly of a series of N-terminal fragments of tau, with no evidence of C-terminal tau fragments. We characterized a subset of high affinity tau antibodies, each capable of engaging and neutralizing eTau. We found that neutralizing eTau reduces Aβ levels in vitro in primary human cortical neurons where exogenously adding eTau increases Aβ levels. In vivo, neutralizing human tau in 2 human tau transgenic models also reduced Aβ levels. We show that the human tau insert sequence is sufficient to cause the observed increase in Aβ levels. Our data furthermore suggest that neuronal hyperactivity may be the mechanism by which this regulation occurs. We show that neuronal hyperactivity regulates both eTau secretion and Aβ production. Electrophysiological analysis shows for the first time that secreted eTau causes neuronal hyperactivity. Its induction of hyperactivity may be the mechanism by which eTau regulates Aβ production. Together with previous findings, these data posit a novel connection between tau and Aβ, suggesting a dynamic mechanism of positive feed forward regulation. Aβ drives the disease pathway through tau, with eTau further increasing Aβ levels, perpetuating a destructive cycle.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Neurons derived from stem cells of patients with familial AD secreted amino-terminal tau fragments, termed e-tau.
“The developers of BMS-986168 observed that neurons derived from stem cells of patients with familial AD secreted amino-terminal tau fragments, termed e-tau215.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [215]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Takahashi, K., Tanabe, K., Ohnuki, M., Narita, M., Ichisaka, T., Tomoda, K., & Yamanaka, S. (2007) · Cell · doi:10.1016/j.cell.2007.11.019 · Cited by 20,221 · see citing works
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484 · see citing works
Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling
Chambers, S. M., Fasano, C. A., Papapetrou, E. P., Tomishima, M., Sadelain, M., & Studer, L. (2009) · Nature Biotechnology · doi:10.1038/nbt.1529 · Cited by 3,620 · see citing works
Staging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357 · see citing works
Dimos, J. T., Rodolfa, K. T., Niakan, K. K., Weisenthal, L. M., Mitsumoto, H., Chung, W. K., Croft, G. F., Saphier, G., Leibel, R. L., Goland, R., et al. (2008) · Science · doi:10.1126/science.1158799 · Cited by 1,959 · see citing works
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892 · see citing works
Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models
Ittner, L. M., Ke, Y. D., Delerue, F., Bi, M., Gladbach, A., van Eersel, J., Wölfing, H., Chieng, B. C., Christie, M. J., Napier, I. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.036 · Cited by 1,821 · see citing works
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644 · see citing works
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611 · see citing works
Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526 · 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
Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371 · see citing works
Synaptic Activity Regulates Interstitial Fluid Amyloid-β Levels In Vivo
Cirrito, J. R., Yamada, K. A., Finn, M. B., Sloviter, R. S., Bales, K. R., May, P. C., Schoepp, D. D., Paul, S. M., Mennerick, S., & Holtzman, D. M. (2005) · Neuron · doi:10.1016/j.neuron.2005.10.028 · Cited by 1,265 · see citing works
Trans-Synaptic Spread of Tau Pathology In Vivo
Liu, L., Drouet, V., Wu, J., Witter, M. P., Small, S. A., Clelland, C. L. T., & Duff, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031302 · Cited by 994 · see citing works
Tau is essential to β-amyloid-induced neurotoxicity
Rapoport, M., Dawson, H. N., Binder, L. I., Vitek, M. P., & Ferreira, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092136199 · Cited by 807 · see citing works
Roberson, E. D., Halabisky, B., Yoo, J. W., Yao, J., Chin, J., Yan, F., Wu, T., Hamto, P., Devidze, N., Yu, G.-Q., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4152-10.2011 · Cited by 654 · see citing works
Physiological release of endogenous tau is stimulated by neuronal activity
Pooler, A. M., Phillips, E. C., Lau, D. H. W., Noble, W., & Hanger, D. P. (2013) · The EMBO Reports · doi:10.1038/embor.2013.15 · Cited by 642 · see citing works
Endocytosis Is Required for Synaptic Activity-Dependent Release of Amyloid-β In Vivo
Cirrito, J. R., Kang, J.-E., Lee, J., Stewart, F. R., Verges, D. K., Silverio, L. M., Bu, G., Mennerick, S., & Holtzman, D. M. (2008) · Neuron · doi:10.1016/j.neuron.2008.02.003 · Cited by 635 · see citing works
Neuronal 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
Schweers, O., Schönbrunn, E., Marx, A., & Mandelkow�, E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)51080-8 · Cited by 569 · see citing works
Tau Reduction Prevents Aβ-Induced Defects in Axonal Transport
Vossel, K. A., Zhang, K., Brodbeck, J., Daub, A. C., Sharma, P., Finkbeiner, S., Cui, B., & Mucke, L. (2010) · Science · doi:10.1126/science.1194653 · Cited by 486 · see citing works
Global Hairpin Folding of Tau in Solution
Jeganathan, S., von Bergen, M., Brutlach, H., Steinhoff, H.-J., & Mandelkow, E. (2006) · Biochemistry · doi:10.1021/bi0521543 · Cited by 432 · see citing works
Yamada, K., Cirrito, J. R., Stewart, F. R., Jiang, H., Finn, M. B., Holmes, B. B., Binder, L. I., Mandelkow, E.-M., Diamond, M. I., Lee, V. M.-Y., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2569-11.2011 · Cited by 351 · see citing works
Tau Protein Is Required for Amyloid β-Induced Impairment of Hippocampal Long-Term Potentiation
Shipton, O. A., Leitz, J. R., Dworzak, J., Acton, C. E. J., Tunbridge, E. M., Denk, F., Dawson, H. N., Vitek, M. P., Wade-Martins, R., Paulsen, O., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2610-10.2011 · Cited by 315 · see citing works
Antisense Reduction of Tau in Adult Mice Protects against Seizures
DeVos, S. L., Goncharoff, D. K., Chen, G., Kebodeaux, C. S., Yamada, K., Stewart, F. R., Schuler, D. R., Maloney, S. E., Wozniak, D. F., Rigo, F., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2107-13.2013 · Cited by 311 · see citing works
A cellular model for sporadic ALS using patient-derived induced pluripotent stem cells
Burkhardt, M. F., Martinez, F. J., Wright, S., Ramos, C., Volfson, D., Mason, M. J., Garnes, J., Dang, V., Lievers, J., Shoukat-Mumtaz, U., et al. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2013.07.007 · Cited by 300 · see citing works
Self-citationMcConlogue, L., Buttini, M., Anderson, J. P., Brigham, E. F., Chen, K. S., Freedman, S. B., Games, D., Johnson-Wood, K., Lee, M., Zeller, M., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611687200 · Cited by 300 · cited 1× · see citing works
“In agreement with the observation that even partial reductions in soluble Ab levels can have a profound impact on the development of Ab pathology (McConlogue et al., 2007), our data identifying secreted eTau fragments and their effect on Ab production are an important step forward to understanding the relationship of…”
Terwel, D., Lasrado, R., Snauwaert, J., Vandeweert, E., Haesendonck, C. V., Borghgraef, P., & LEUVEN, F. V. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409876200 · Cited by 267 · 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
Spatial and temporal relationships between plaques and tangles in Alzheimer-pathology
Schönheit, B., Zarski, R., & Ohm, T. G. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.09.009 · Cited by 262 · see citing works
Dujardin, S., Lécolle, K., Caillierez, R., Bégard, S., Zommer, N., Lachaud, C., Carrier, S., Dufour, N., Aurégan, G., Winderickx, J., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-14 · Cited by 259 · see citing works
Holth, J. K., Bomben, V. C., Reed, J. G., Inoue, T., Younkin, L., Younkin, S. G., Pautler, R. G., Botas, J., & Noebels, J. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3191-12.2013 · Cited by 238 · 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
Characterization of Novel CSF Tau and ptau Biomarkers for Alzheimer’s Disease
Meredith Jr., J. E., Sankaranarayanan, S., Guss, V., Lanzetti, A. J., Berisha, F., Neely, R. J., Slemmon, J. R., Portelius, E., Zetterberg, H., Blennow, K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076523 · Cited by 209 · see citing works
Ribé, E. M., Pérez, M., Puig, B., Gich, I., Lim, F., Cuadrado, M., Sesma, T., Catena, S., Sánchez, B., Nieto, M., et al. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.05.027 · Cited by 162 · see citing works
Braak, H., Zetterberg, H., Tredici, K. D., & Blennow, K. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1139-0 · Cited by 141 · see citing works
Alzheimer’s disease: intraneuronal alterations precede insoluble amyloid-β formation
Braak, H., & Tredici, K. D. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.12.015 · Cited by 85 · see citing works
Colombo, A. V., Wang, H., Kuhn, P., Page, R., Kremmer, E., Dempsey, P. J., Crawford, H. C., & Lichtenthaler, S. F. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.08.011 · Cited by 76 · see citing works
Opposing Synaptic Regulation of Amyloid-β Metabolism by NMDA Receptors <i>In Vivo</i>
Verges, D. K., Restivo, J. L., Goebel, W. D., Holtzman, D. M., & Cirrito, J. R. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0607-11.2011 · Cited by 74 · see citing works
Perlecan domain V inhibits α2 integrin-mediated amyloid-β neurotoxicity
Wright, S., Parham, C. L., Lee, B., Clarke, D. N., Auckland, L. D., Johnston, J. A., Lawrence, A. L., Dickeson, S. K., Santoro, S. A., Griswold‐Prenner, I., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.10.018 · Cited by 19 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Induced pluripotent stem cell technology: a decade of progress.
Shi, Y., Inoue, H., Wu, J. C., & Yamanaka, S. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.245 · Cited by 1,525 · 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
Nguyen, P. H., Ramamoorthy, A., Sahoo, B. R., Zheng, J., Faller, P., Straub, J. E., Domı́nguez, L., Shea, J., Dokholyan, N. V., Simone, A. D., et al. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01122 · Cited by 676 · see citing works
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
Tau Kinetics in Neurons and the Human Central Nervous System
Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.015 · Cited by 586 · see citing works
Boxer, A. L., Yu, J.-T., Golbe, L. I., Litvan, I., Lang, A. E., & Höglinger, G. U. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30157-6 · Cited by 485 · see citing works
Tau-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
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
Tau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies
Chang, C.-W., Shao, E., & Mucke, L. (2021) · Science · doi:10.1126/science.abb8255 · Cited by 263 · 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
Stem Cells in the Treatment of Disease.
Blau, H., & Daley, G. (2019) · New England Journal of Medicine · doi:10.1056/nejmra1716145 · Cited by 182 · see citing works
Rösler, T. W., Marvian, A. T., Brendel, M., Nykänen, N.-P., Höllerhage, M., Schwarz, S. C., Hopfner, F., Koeglsperger, T., Respondek, G., Schweyer, K., et al. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101644 · Cited by 219 · see citing works
Omole, A. E., & Fakoya, A. O. J. (2018) · PeerJ · doi:10.7717/peerj.4370 · Cited by 207 · see citing works
Induced pluripotent stem cells: at the heart of cardiovascular precision medicine
Chen, I. Y., Matsa, E., & Wu, J. C. (2016) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.36 · Cited by 191 · see citing works
Accelerating Alzheimer’s therapeutic development: The past and future of clinical trials
Boxer, A. L., & Sperling, R. (2023) · Cell · doi:10.1016/j.cell.2023.09.023 · Cited by 197 · see citing works
Tau-Centric targets and drugs in clinical development for the treatment of alzheimer's disease
Panza, F., Solfrizzi, V., Seripa, D., Imbimbo, B. P., Lozupone, M., Santamato, A., Zecca, C., Barulli, M. R., Bellomo, A., Pilotto, A., et al. (2016) · BioMed Research International · doi:10.1155/2016/3245935 · Cited by 195 · see citing works
Evans, L., Wassmer, T., Fraser, G. M., Smith, J. C., Perkinton, M. S., Billinton, A., & Livesey, F. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.021 · Cited by 187 · 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
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
Detection of Aggregation-Competent Tau in Neuron-Derived Extracellular Vesicles
Guix, F. X., Corbett, G. T., Cha, D., Mustapić, M., Liu, W., Mengel, D., Chen, Z., Aïkawa, E., Young‐Pearse, T. L., Kapogiannis, D., et al. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030663 · Cited by 182 · see citing works
Kanmert, D., Cantlon, A., Muratore, C., Jin, M., O’Malley, T. T., Lee, G. S., Young‐Pearse, T. L., Selkoe, D. J., & Walsh, D. M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.0387-15.2015 · Cited by 159 · see citing works
Passive immunotherapies targeting Aβ and tau in Alzheimer's disease
Plotkin, S. S., & Cashman, N. R. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105010 · Cited by 156 · see citing works
An Overview on the Clinical Development of Tau-Based Therapeutics
Medina, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041160 · Cited by 156 · see citing works
Rajasekhar, K., & Govindaraju, T. (2018) · RSC Advances · doi:10.1039/c8ra03620a · Cited by 150 · see citing works
Novak, P., Schmidt, R., Kontsekova, E., Kovacech, B., Smolek, T., Katina, S., Fialova, L., Prcina, M., Parrak, V., Dal-Bianco, P., et al. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0436-1 · Cited by 147 · see citing works
Dam, T., Boxer, A. L., Golbe, L. I., Höglinger, G. U., Morris, H. R., Litvan, I., Lang, A. E., Corvol, J., Aiba, I., Grundman, M., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01455-x · Cited by 146 · 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
Complex Tissue and Disease Modeling using hiPSCs
Passier, R., Orlova, V., & Mummery, C. (2016) · Cell Stem Cell · doi:10.1016/j.stem.2016.02.011 · Cited by 142 · see citing works
Stem Cells, Genome Editing, and the Path to Translational Medicine
Soldner, F., & Jaenisch, R. (2018) · Cell · doi:10.1016/j.cell.2018.09.010 · Cited by 139 · see citing works
Evolving concepts in progressive supranuclear palsy and other 4-repeat tauopathies
Stamelou, M., Respondek, G., Giagkou, N., Whitwell, J. L., Kovács, G. G., & Höglinger, G. U. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-021-00541-5 · Cited by 143 · see citing works
Boxer, A., Qureshi, I., Ahlijanian, M., Grundman, M., Golbe, L., Litvan, I., Honig, L. S., Tuite, P., McFarland, N. R., O'Suilleabhain, P., et al. (2019) · Lancet Neurology · doi:10.1016/s1474-4422(19)30139-5 · Cited by 115 · see citing works
Tau pathology in neurodegenerative disease: disease mechanisms and therapeutic avenues
Samudra, N. P., Lane‐Donovan, C., VandeVrede, L. A., & Boxer, A. L. (2023) · Journal of Clinical Investigation · doi:10.1172/jci168553 · Cited by 135 · see citing works
Kurbatskaya, K., Phillips, E. C., Croft, C. L., Dentoni, G., Hughes, M. M., Wade, M. A., Al-Sarraj, S., Troakes, C., O'Neill, M., Perez-Nievas, B., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0299-2 · Cited by 132 · see citing works
New Insights Into Drug Discovery Targeting Tau Protein
Soeda, Y., & Takashima, A. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.590896 · Cited by 133 · see citing works
Valera, E., Spencer, B. J., & Masliah, E. (2015) · Neurotherapeutics · doi:10.1007/s13311-015-0397-z · Cited by 129 · see citing works
Courade, J., Angers, R. C., Mairet‐Coello, G., Pacico, N., Tyson, K. L., Lightwood, D. J., Munro, R., McMillan, D., Griffin, R., BAKER, T. S., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1911-2 · Cited by 131 · see citing works
Development of disease-modifying drugs for frontotemporal dementia spectrum disorders
Panza, F., Lozupone, M., Seripa, D., Daniele, A., Watling, M., Giannelli, G., & Imbimbo, B. P. (2020) · Nature Reviews Neurology · doi:10.1038/s41582-020-0330-x · Cited by 122 · see citing works
Synaptic tau: A pathological or physiological phenomenon?
Robbins, M., Clayton, E. L., & Schierle, G. S. K. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01246-y · Cited by 117 · see citing works
Progressive supranuclear palsy: Advances in diagnosis and management
Coughlin, D. G., & Litvan, I. (2020) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2020.04.014 · Cited by 113 · see citing works
Dai, C.-L., Hu, W., Tung, Y. C., Liu, F., Gong, C.-X., & Iqbal, K. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0341-7 · Cited by 99 · see citing works
Tau-Based Therapeutics for Alzheimer’s Disease: Active and Passive Immunotherapy
Panza, F., Solfrizzi, V., Seripa, D., Imbimbo, B. P., Lozupone, M., Santamato, A., Tortelli, R., Galizia, I., Prete, C., Daniele, A., et al. (2016) · Immunotherapy · doi:10.2217/imt-2016-0019 · Cited by 105 · see citing works
Ondrejčák, T., Klyubin, I. V., Corbett, G. T., Fraser, G. M., Hong, W., Mably, A. J., Gardener, M. J., Hammersley, J., Perkinton, M. S., Billinton, A., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1700-18.2018 · Cited by 102 · see citing works
Possible Mechanisms of Tau Spread and Toxicity in Alzheimer’s Disease
Zhang, H., Cao, Y., Ma, L., Wei, Y., & Li, H. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.707268 · Cited by 104 · see citing works
Targeting tau: clinical trials and novel therapeutic approaches
VandeVrede, L., Boxer, A. L., & Polydoro, M. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134919 · Cited by 90 · 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
Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets
Kwon, S., Iba, M., Kim, C., & Masliah, E. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00853-2 · Cited by 92 · see citing works
Zhang, Z., Li, X., Wang, Z.-H., Song, M., Yu, S. P., Kang, S. S., Liu, X., Zhang, Z., Xie, M., Liu, G., et al. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0286-z · Cited by 90 · see citing works
A randomized, single ascending dose study of intravenous BIIB092 in healthy participants
Qureshi, I., Tirucherai, G., Ahlijanian, M. K., Kolaitis, G., Bechtold, C. M., & Grundman, M. (2018) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.10.007 · Cited by 90 · 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
The role of APOE4 in Alzheimer’s disease: strategies for future therapeutic interventions
Hunsberger, H. C., Pinky, P. D., Smith, W., Suppiramaniam, V., & Reed, M. N. (2019) · Neuronal Signaling · doi:10.1042/ns20180203 · Cited by 94 · see citing works
Park, S.-S., Park, H.-S., Kim, C., Kang, H., Kim, D., Baek, S., & Kim, T.-W. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00631-4 · Cited by 89 · see citing works
Ten Years of Tau-Targeted Immunotherapy: The Path Walked and the Roads Ahead
Novak, P., Kontsekova, E., Zilka, N., & Novak, M. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00798 · Cited by 87 · see citing works
Extracellular Tau and Its Potential Role in the Propagation of Tau Pathology
Yamada, K. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00667 · Cited by 84 · see citing works
Tau and MAPT genetics in tauopathies and synucleinopathies
Léveillé, E., Ross, O. A., & Gan‐Or, Z. (2021) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2021.09.008 · Cited by 83 · see citing works
Hu, N., Corbett, G. T., Moore, S., Klyubin, I. V., O’Malley, T. T., Walsh, D. M., Livesey, F. J., & Rowan, M. J. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.040 · Cited by 81 · see citing works
The Neurotoxic Role of Extracellular Tau Protein
Sebastián‐Serrano, Á., de Diego-García, L., & Dı́az-Hernández, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19040998 · Cited by 81 · see citing works
Current directions in tau research: Highlights from Tau 2020
Sexton, C. E., Snyder, H. M., Beher, D., Boxer, A. L., Brannelly, P., Brion, J., Buée, L., Cacace, A. M., Chételat, G., Citron, M., et al. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12452 · Cited by 78 · see citing works
Eisele, Y. S., & Duyckaerts, C. J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1516-y · Cited by 78 · see citing works
Sigurdsson, E. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179937 · Cited by 76 · see citing works
Potential use of antioxidants for the treatment of chronic inflammatory diseases
Blagov, A. V., Summerhill, V. I., Sukhorukov, V. N., Zhigmitova, E. B., Postnov, A. Y., & Orekhov, A. N. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1378335 · Cited by 72 · see citing works
Boxer, A. L., Gold, M., Feldman, H., Boeve, B. F., Dickinson, S. L.-J., Fillit, H., Ho, C., Paul, R., Pearlman, R., Sutherland, M., et al. (2020) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2019.06.4956 · Cited by 71 · see citing works
Latimer, C., Keene, C., Flanagan, M. E., Hemmy, L., Lim, K. O., White, L. R., Montine, K., & Montine, T. (2017) · Journal of Neuropathology and Experimental Neurology · doi:10.1093/jnen/nlx030 · Cited by 71 · see citing works
Tau immunotherapies for Alzheimer’s disease
Hoskin, J. L., Sabbagh, M. N., Al-Hasan, Y. M., & Decourt, B. (2019) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2019.1619694 · Cited by 68 · see citing works
Tau 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
Osorio, R. S., Ducca, E. L., Wohlleber, M. E., Tanzi, E. B., Gumb, T., Twumasi, A., Tweardy, S., Lewis, C., Fischer, E., Koushyk, V., et al. (2016) · SLEEP · doi:10.5665/sleep.5846 · Cited by 64 · see citing works
Morozova, V., Cohen, L. S., Makki, A. E.-H., Shur, A., Pilar, G. R., Idrissi, A. E., & Alonso, A. D. C. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00403 · Cited by 64 · see citing works
Characterization of tau binding by gosuranemab
Sopko, R., Golonzhka, O., Arndt, J. W., Quan, C., Czerkowicz, J., Cameron, A., Smith, B., Yogapriya, M., Gibbons, G. S., Kim, S., et al. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105120 · Cited by 64 · see citing works
Rubinski, A., Franzmeier, N., Neitzel, J., Ewers, M., & (ADNI), T. A. D. N. I. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00702-6 · Cited by 63 · see citing works
Passive immunotherapy for Alzheimer's disease
Guo, X., Li, Y., Zhang, D., & Zhao, Y. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102192 · Cited by 66 · see citing works
Tau-targeting therapy in Alzheimer’s disease: Critical advances and future opportunities
Guo, Y., Li, S., Zeng, L.-H., & Tan, J. (2022) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2022.16 · Cited by 61 · see citing works
Tau Filament Self-Assembly and Structure: Tau as a Therapeutic Target
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
Tau Secretion: Good and Bad for Neurons
Pernègre, C., Duquette, A., & Leclerc, N. M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00649 · Cited by 62 · see citing works
Croft, C. L., Wade, M. A., Kurbatskaya, K., Mastrandreas, P., Hughes, M. M., Phillips, E. C., Pooler, A. M., Perkinton, M. S., Hanger, D. P., & Noble, W. J. (2017) · Cell Death and Disease · doi:10.1038/cddis.2017.97 · Cited by 59 · see citing works
Cerebrospinal fluid ratios with Aβ 42 predict preclinical brain β‐amyloid accumulation
Racine, A. M., Koscik, R. L., Nicholas, C. R. N., Clark, L. R., Okonkwo, O. C., Oh, J. M., Hillmer, A. T., Murali, D., Barnhart, T. E., Betthauser, T. J., et al. (2015) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2015.11.006 · Cited by 58 · see citing works
Sigurdsson, E. M. (2016) · Neurodegenerative Diseases · doi:10.1159/000440842 · Cited by 56 · see citing works
Progress in Target Drug Molecules for Alzheimer's Disease
Xie, J., Liang, R., Wang, Y., Huang, J., Cao, X., & Niu, B. (2019) · Current Topics in Medicinal Chemistry · doi:10.2174/1568026619666191203113745 · Cited by 57 · see citing works
Cerebrospinal fluid biomarkers predict frontotemporal dementia trajectory
Ljubenkov, P. A., Staffaroni, A. M., Rojas, J. C., Allen, I. E., Wang, P., Heuer, H., Karydas, A., Kornak, J., Cobigo, Y., Seeley, W. W., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.643 · Cited by 49 · see citing works
Florenzano, F., Corsetti, V., Ciasca, G., Ciotti, M. T., Pittaluga, A., Olivero, G., Feligioni, M., Iannuzzi, F., Latina, V., Sciacca, M. F. M., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.17371 · Cited by 52 · see citing works
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
Tau secretion is correlated to an increase of Golgi dynamics
Mohamed, N., Desjardins, A., & Leclerc, N. M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0178288 · Cited by 50 · see citing works
Four-Repeat Tauopathies: Current Management and Future Treatments
VandeVrede, L. A., Ljubenkov, P. A., Rojas, J. C., Welch, A. E., & Boxer, A. L. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00888-5 · Cited by 53 · see citing works
Tau-directed approaches for the treatment of Alzheimer’s disease: focus on leuco-methylthioninium
Seripa, D., Solfrizzi, V., Imbimbo, B. P., Daniele, A., Santamato, A., Lozupone, M., Zuliani, G., Greco, A., Logroscino, G., & Panza, F. (2016) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.2016.1140039 · Cited by 50 · see citing works
Initiative, A. D. N., Halawa, O. A., Gatchel, J. R., Amariglio, R. E., Rentz, D. M., Sperling, R. A., Johnson, K. A., & Marshall, G. A. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0471-6 · Cited by 50 · see citing works
Tau Spreading Mechanisms; Implications for Dysfunctional Tauopathies
Fuster-Matanzo, A., Hernández, F., & Ávila, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030645 · Cited by 48 · see citing works
NPT088 reduces both amyloid‐β and tau pathologies in transgenic mice
Levenson, J. M., Schroeter, S., Carroll, J. C., Cullen, V., Asp, E., Proschitsky, M., Chung, C. H. ‐., Gilead, S., Nadeem, M., Dodiya, H. B., et al. (2016) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2016.06.004 · Cited by 47 · see citing works
Recent Updates on Induced Pluripotent Stem Cells in Hematological Disorders
Wattanapanitch, M. (2019) · Stem Cells International · doi:10.1155/2019/5171032 · Cited by 45 · see citing works
Feasibility of short imaging protocols for [18F]PI-2620 tau-PET in progressive supranuclear palsy
Song, M., Scheifele, M., Barthel, H., van Eimeren, T., Beyer, L., MAREK, K. L., Eckenweber, F., Palleis, C., Kaiser, L., Finze, A., et al. (2021) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-021-05391-3 · Cited by 46 · see citing works
Tau immunotherapy is associated with glial responses in FTLD-tau
Kim, B., Mikytuck, B., Suh, E. R., Gibbons, G. S., Deerlin, V. M. V., Vaishnavi, S., Spindler, M., Massimo, L. M., Grossman, M., Trojanowski, J. Q., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02318-y · Cited by 46 · 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
Delta-secretase cleavage of Tau mediates its pathology and propagation in Alzheimer’s disease
Kang, S. S., Ahn, E. H., & Ye, K. (2020) · Experimental & Molecular Medicine · doi:10.1038/s12276-020-00494-7 · Cited by 45 · see citing works
Recent advancements toward therapeutic vaccines against Alzheimer’s disease
Herline, K., Drummond, E., & Wısnıewskı, T. (2018) · Expert Review of Vaccines · doi:10.1080/14760584.2018.1500905 · Cited by 44 · see citing works
Amadoro, G., Latina, V., Corsetti, V., & Calissano, P. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2019.165584 · Cited by 42 · see citing works
Corsetti, V., Borreca, A., Latina, V., Giacovazzo, G., Pignataro, A., Krashia, P., Natale, F., Cocco, S., Rinaudo, M., Malerba, F., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa039 · Cited by 41 · see citing works
Early investigational drugs targeting tau protein for the treatment of Alzheimer’s disease
Anand, K., & Sabbagh, M. N. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.1075002 · Cited by 41 · see citing works
Congdon, E. E., Jiang, Y., & Sigurdsson, E. M. (2021) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2021.12.002 · Cited by 37 · see citing works
Knockin’ on heaven’s door: Molecular mechanisms of neuronal tau uptake
La‐Rocque, S. D., Moretto, E., Butnaru, I., & Schiavo, G. (2020) · Journal of Neurochemistry · doi:10.1111/jnc.15144 · Cited by 42 · see citing works
The propagation mechanisms of extracellular tau in Alzheimer’s disease
Wei, Y., Liu, M., & Wang, D. (2021) · Journal of Neurology · doi:10.1007/s00415-021-10573-y · Cited by 39 · see citing works
Tau Conformation as a Target for Disease-Modifying Therapy: The Role of Truncation
Novák, P., Cehlár, O., Škrabana, R., & Novák, M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179942 · Cited by 36 · see citing works
Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative review
Chu, D., Yang, X., Wang, J., Zhou, Y., Gu, J., Miao, J., Wu, F., & Liu, F. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385853 · Cited by 37 · see citing works
Jacquet, A. D. R., Denis, H. L., Cicchetti, F., & Alpaugh, M. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00999-7 · Cited by 35 · see citing works
- Authors
- Bright, J., Hussain, S., Dang, V., Wright, S., Cooper, B., Byun, T., Ramos, C., Singh, A., Parry, G., Stagliano, N., & Griswold-Prenner, I.
- Corresponding author
- Stagliano, Nancy
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 36
- Issue
- 2
- Pages
- 693-709
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2044321001
- Cited by
- 230
- References
- 41
- Citations by year
- 2026: 5 · 2025: 13 · 2024: 11 · 2023: 17 · 2022: 16 · 2021: 26 · 2020: 31 · 2019: 30 · 2018: 43 · 2017: 12 · 2016: 17 · 2015: 9
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neurobiology of Aging (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- 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
- amyloid-beta production, Alzheimer's disease, neuronal hyperactivity, cortical neurons, amyloid precursor protein transgenic mice, positive feedback loop
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, Cerebral Cortex, Chromatography, Liquid, Humans, Mice, Transgenic, Neurons, Mass Spectrometry, Amyloid beta-Peptides, tau Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
