Passive Immunization with Tau Oligomer Monoclonal Antibody Reverses Tauopathy Phenotypes without Affecting Hyperphosphorylated Neurofibrillary Tangles
Open accessAbstract
Recent findings suggest that tau oligomers, which form before neurofibrillary tangles (NFTs), are the true neurotoxic tau entities in neurodegenerative tauopathies, including Alzheimer's disease (AD). Studies in animal models of tauopathy suggest that tau oligomers play a key role in eliciting behavioral and cognitive impairments. Here, we used a novel tau oligomer-specific monoclonal antibody (TOMA) for passive immunization in mice expressing mutant human tau. A single dose of TOMA administered either intravenously or intracerebroventricularly was sufficient to reverse both locomotor and memory deficits in a mouse model of tauopathy for 60 d, coincident with rapid reduction of tau oligomers but not phosphorylated NFTs or monomeric tau. Our data demonstrate that antibody protection is mediated by extracellular and rapid peripheral clearance. These findings provide the first direct evidence in support of a critical role for tau oligomers in disease progression and validate tau oligomers as a target for the treatment of AD and other neurodegenerative tauopathies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Elevated levels of TauO are present in the brain, cerebrospinal fluid, and sera from Alzheimer's disease patients with clinical severity.
“we observed elevated levels of TauO in the brain, cerebrospinal fluid (CSF), and sera from AD patients with clinical severity, 9 , 15 , 16 , 17 , 18 , 19 , 20”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [16]
Novel anti-tau antibodies specifically recognize disease-relevant tau strains and conformations.
“significant advancements have been made in the development of novel anti‐tau antibodies that specifically recognize disease‐relevant tau strains and conformations.”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [16]
These anti-tau antibodies target unique conformational epitopes independent of specific linear amino acid sequences and exhibit preferences for different subsets of tau oligomers.
“These antibodies target unique conformational epitopes, independent of specific linear amino acid sequences, and exhibit preferences for different subsets of tau oligomers.”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [16]
Monoclonal antibodies against the amino-terminal or repeat domain (306-320) region, oligomeric tau, misfolded tau, pSer202, pThr231, pSer409, pSer413 and pSer422 have proved to be efficacious in tauopathy models.
“In addition, monoclonal antibodies against the amino-terminal or repeat domain (306–320) region209–215, oligomeric tau216,217, misfolded tau201,218,219, pSer202220,221, pThr231208 pSer409222, pSer413223 and pSer422224 have proved to be efficacious in tauopathy models.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [216]
Several reports are available of antibodies that are capable of reducing tau levels and preventing spreading without apparently entering neurons.
“Indeed, several reports are available of antibodies that are capable of reducing tau levels and preventing spreading without apparently entering neurons216,218,239.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [216]
Cites
1 retracted
Masliah, E., Rockenstein, E. M., Mante, M., Crews, L. A., Spencer, B. J., Adame, A., Patrick, C., Trejo, M., Ubhi, K. K., Rohn, T. T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019338 · Cited by 422 · cited 5× · see citing works
“…exclusive and it has been demonstrated that different clearance mechanisms can be activated to different degrees depending on the antibody and its target (DeMattos et al., 2001; Levites et al., 2006; Sigurdsson, 2008; Golde et al., 2009; Masliah et al., 2011; Morgan, 2011; Ubhi and Masliah, 2011).”
BackgroundInfluentialRetractedSynapse 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 · cited 1× · see citing works
“…metastable tau aggregates such as NFTs are not causally linked to tauopathy phenotypes in animal models (Wittmann et al., 2001; Santacruz et al., 2005; Berger et al., 2007; Yoshiyama et al., 2007; Polydoro et al., 2009; LasagnaReeves et al., 2011b; Spires-Jones et al., 2011; Cowan et al., 2012).”
BackgroundTau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174 · cited 3× · see citing works
“In addition, tau mutations can cause disorders such as familial frontotemporal dementia (for review, see Ballatore et al., 2007).”
BackgroundInfluentialTau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014 · see citing works
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012 · 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
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · cited 1× · see citing works
“…human AD brain, NFT-containing neurons can survive for decades (Morsch et al., 1999) and neuronal loss precedes or is independent of NFT formation (Gómez-Isla et al., 1997; Terry, 2000; Maeda et al., 2006; van de Nes et al., 2008), suggesting that other tau species may contribute to earlier…”
BackgroundLewis, 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 · cited 3× · see citing works
“The JNPL3 mouse model (Lewis et al., 2000) expresses a frontotemporal dementia-associated human mutant tau transgene (P301L) and has been used previously for tau immunotherapy (Asuni et al., 2007; Chai et al., 2011; Bi et al., 2011).”
MethodDeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J.-C., Paul, S. M., & Holtzman, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151261398 · Cited by 1,298 · see citing works
Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998 · see citing works
Tauopathy in <i>Drosophila</i> : Neurodegeneration Without Neurofibrillary Tangles
Wittmann, C. W., Wszolek, M. F., Shulman, J. M., Salvaterra, P. M., Lewis, J., Hutton, M., & Feany, M. B. (2001) · Science · doi:10.1126/science.1062382 · Cited by 939 · cited 1× · see citing works
“…body of evidence suggests that large, metastable tau aggregates such as NFTs are not causally linked to tauopathy phenotypes in animal models (Wittmann et al., 2001; Santacruz et al., 2005; Berger et al., 2007; Yoshiyama et al., 2007; Polydoro et al., 2009; LasagnaReeves et al., 2011b;…”
BackgroundTau 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
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
Prion-like mechanisms in neurodegenerative diseases
Frost, B., & Diamond, M. I. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2786 · Cited by 776 · see citing works
Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Clos, A. L., Jackson, G. R., & Kayed, R. (2011) · Molecular Neurodegeneration · doi:10.1186/1750-1326-6-39 · Cited by 633 · see citing works
Self-citationYanamandra, K., Kfoury, N., Jiang, H., Mahan, T. E., Ma, S., Maloney, S. E., Wozniak, D. F., Diamond, M. I., & Holtzman, D. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.046 · Cited by 574 · see citing works
Trans-cellular Propagation of Tau Aggregation by Fibrillar Species
Kfoury, N., Holmes, B. B., Jiang, H., Holtzman, D. M., & Diamond, M. I. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.346072 · Cited by 552 · cited 1× · see citing works
“As described recently in cell culture experiments, anti-tau antibodies can trap tau aggregates in the extracellular space and thus prevent the uptake and propagation of tau in adjacent cells (Kfoury et al., 2012).”
BackgroundEffects 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
Wu, J. W., Herman, M., Liu, L., Simoes, S., Acker, C. M., Figueroa, H., Steinberg, J. I., Margittai, M., Kayed, R., Zurzolo, C., et al. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.394528 · Cited by 537 · cited 3× · see citing works
“, tau oligomeric intermediates) in tauopathies is poorly understood; however, novel polyclonal and monoclonal antibodies that define specific tau species have enabled the study of tau oligomers in vivo (Patterson et al., 2011; Lasagna-Reeves et al., 2012a; Blair et al., 2013; Hawkins et al., 2013; Wu et al., 2013).”
BackgroundSelf-citationIdentification of oligomers at early stages of tau aggregation in Alzheimer's disease
Lasagna‐Reeves, C. A., Castillo‐Carranza, D. L., Sengupta, U., Sarmiento, J., Troncoso, J., Jackson, G. R., & Kayed, R. (2012) · The FASEB Journal · doi:10.1096/fj.11-199851 · Cited by 527 · cited 29× · see citing works
“We also showed that AD-brain-derived tau oligomers isolated using T22 disrupt memory and propagate the abnormal conformation of endogenous tau in wild-type mice, implicating tau oligomers in the spread of pathology but not NFTs (Lasagna-Reeves et al., 2012b).”
BackgroundMethodResultInfluentialSelf-citationAsuni, A. A., Boutajangout, A., Quartermain, D., & Sigurdsson, E. M. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2361-07.2007 · Cited by 506 · cited 8× · see citing works
“A possible explanation for this is that previous studies (Asuni et al., 2007; Boimel et al., 2010; Boutajangout et al., 2011; Chai et al., 2011; Gu and Sigurdsson, 2011; Bi et al., 2011) specifically targeted tau pathology using phosphorylated antigens or antibodies directed against p-epitopes…”
BackgroundMethodResultInfluentialAlzheimer 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
Self-citationAccumulation of Pathological Tau Species and Memory Loss in a Conditional Model of Tauopathy
Berger, Z., Roder, H. M., Hanna, A., Carlson, A. M., Rangachari, V., Yue, M., Wszołek, Z. K., Ashe, K. H., Knight, J. A., Dickson, D. W., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0587-07.2007 · Cited by 485 · cited 1× · see citing works
“…metastable tau aggregates such as NFTs are not causally linked to tauopathy phenotypes in animal models (Wittmann et al., 2001; Santacruz et al., 2005; Berger et al., 2007; Yoshiyama et al., 2007; Polydoro et al., 2009; LasagnaReeves et al., 2011b; Spires-Jones et al., 2011; Cowan et al., 2012).”
BackgroundTai, H., Serrano‐Pozo, A., Hashimoto, T., Frosch, M. P., Spires‐Jones, T. L., & Hyman, B. T. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.06.033 · Cited by 456 · cited 2× · see citing works
“, 2012), impairing the ubiquitin-proteasome system (Tai et al., 2012) and contributing to synaptic dysfunction and loss.”
BackgroundNeurons May Live for Decades with Neurofibrillary Tangles
Morsch, R., Simon, W., & Coleman, P. D. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199902000-00008 · Cited by 370 · cited 2× · see citing works
“Furthermore, in human AD brain, NFT-containing neurons can survive for decades (Morsch et al., 1999) and neuronal loss precedes or is independent of NFT formation (Gómez-Isla et al., 1997; Terry, 2000; Maeda et al., 2006; van de Nes et al., 2008), suggesting that other tau species may contribute…”
BackgroundPreparation and Characterization of Neurotoxic Tau Oligomers
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Jackson, G. R., & Kayed, R. (2010) · Biochemistry · doi:10.1021/bi1016233 · Cited by 359 · see citing works
Self-citationCharacterization of Prefibrillar Tau Oligomers in Vitro and in Alzheimer Disease
Patterson, K. R., Remmers, C. L., Fu, Y., Brooker, S. M., Kanaan, N. M., Vana, L., Ward, S., Reyes, J. F., Philibert, K., Glucksman, M., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.237974 · Cited by 354 · cited 4× · see citing works
“The therapeutic effects of the TOMA antibody in P301L results in a reduction of pathogenic tau oligomers coinciding with the rescue of tauopathy-related motor and cognitive phenotypes in mice, reinforcing the concept that oligomers are the pathological form of tau in animal models of neurodegenerative tauopathy (Lasag…”
BackgroundInfluentialHolcomb, L. A., Gordon, M. N., Jantzen, P., Hsiao, K., Duff, K., & Morgan, D. (1999) · Behavior Genetics · doi:10.1023/a:1021691918517 · Cited by 353 · cited 1× · see citing works
“To determine the effect of immunotherapy on behavioral deficits, the spatial memory and motor function of P301L and wildtype mice were evaluated by rotarod and Y-maze tests (Holcomb et al., 1999; Morgan et al., 2008).”
MethodPassive 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
Antibody-Aided Clearance of Extracellular α-Synuclein Prevents Cell-to-Cell Aggregate Transmission
Bae, E.-J., Lee, H.-J., Rockenstein, E., Ho, D.-H., Park, E.-B., Yang, N.-Y., Desplats, P., Masliah, E., & Lee, S.-J. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1292-12.2012 · Cited by 339 · cited 1× · see citing works
“Moreover, another study demonstrated that the clearance of extracellular -synuclein by passive immunization prevents cell-to-cell aggregate transmission and ameliorates neurodegeneration and behavioral deficits (Bae et al., 2012; Yanamandra et al., 2013).”
BackgroundAge-Dependent Impairment of Cognitive and Synaptic Function in the htau Mouse Model of Tau Pathology
Polydoro, M., Acker, C. M., Duff, K., Castillo, P. E., & Davies, P. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1065-09.2009 · Cited by 329 · cited 1× · see citing works
“…metastable tau aggregates such as NFTs are not causally linked to tauopathy phenotypes in animal models (Wittmann et al., 2001; Santacruz et al., 2005; Berger et al., 2007; Yoshiyama et al., 2007; Polydoro et al., 2009; LasagnaReeves et al., 2011b; Spires-Jones et al., 2011; Cowan et al., 2012).”
BackgroundAccelerated neurodegeneration through chaperone-mediated oligomerization of tau
Blair, L. J., Nordhues, B. A., Hill, S. E., Scaglione, K. M., O’Leary, J. C., Fontaine, S. N., Breydo, L., Zhang, B., Li, P., Wang, L., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69003 · Cited by 322 · cited 2× · see citing works
“, tau oligomeric intermediates) in tauopathies is poorly understood; however, novel polyclonal and monoclonal antibodies that define specific tau species have enabled the study of tau oligomers in vivo (Patterson et al., 2011; Lasagna-Reeves et al., 2012a; Blair et al., 2013; Hawkins et al., 2013; Wu et al., 2013).”
BackgroundSelf-citationBoutajangout, A., Ingadottir, J., Davies, P., & Sigurdsson, E. M. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07337.x · Cited by 306 · cited 3× · see citing works
“The dose used in this study was 5- to 10-fold lower than those previously used to nonselectively target tau aggregates by passive immunotherapy (Boutajangout et al., 2011; Chai et al., 2011), which may also contribute to increased safety while maintaining efficacy because oligomers represent a small percentage of tota…”
BackgroundMethodIncreased levels of granular tau oligomers: An early sign of brain aging and Alzheimer's disease
Maeda, S., Sahara, N., Saito, Y., Murayama, S., Ikai, A., & Takashima, A. (2006) · Neuroscience Research · doi:10.1016/j.neures.2005.11.009 · Cited by 301 · cited 1× · see citing works
“…NFT-containing neurons can survive for decades (Morsch et al., 1999) and neuronal loss precedes or is independent of NFT formation (Gómez-Isla et al., 1997; Terry, 2000; Maeda et al., 2006; van de Nes et al., 2008), suggesting that other tau species may contribute to earlier stages of disease.”
BackgroundWilcock, D. M., Rojiani, A. M., Rosenthal, A., Levkowitz, G., Subbarao, S., Alamed, J., Wilson, D. H., Wilson, N., Freeman, M. J., Gordon, M. N., et al. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1090-04.2004 · Cited by 298 · see citing works
Blood–brain barrier impairment in Alzheimer disease
Bowman, G. L., Kaye, J. A., Moore, M., Waichunas, D., Carlson, N. E., & Quinn, J. F. (2007) · Neurology · doi:10.1212/01.wnl.0000262031.18018.1a · Cited by 294 · see citing works
Template-assisted filament growth by parallel stacking of tau
Margittai, M., & Langen, R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401911101 · Cited by 276 · see citing works
Wilcock, D. M., DiCarlo, G., Henderson, D., Jackson, J., Clarke, K., Ugen, K. E., Gordon, M. N., & Morgan, D. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-09-03745.2003 · Cited by 232 · see citing works
Immunotherapy for Alzheimer’s disease: Key Symposium: Immunotherapy for Alzheimer’s disease
Morgan, D. (2011) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2010.02315.x · Cited by 225 · see citing works
Ma, Q., Zuo, X., Yang, F., Ubeda, O. J., Gant, D. J., Alaverdyan, M., Teng, E., Hu, S., Chen, P., Maiti, P., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.393751 · Cited by 212 · cited 1× · see citing works
“Furthermore, it has been reported that reduction of soluble tau oligomers after treatment with curcumin rescues synaptic and behavioral deficits in aged tau transgenic mice (Ma et al., 2013).”
BackgroundInflammation Induced by Infection Potentiates Tau Pathological Features in Transgenic Mice
Sy, M., Kitazawa, M., Medeiros, R., Whitman, L., Cheng, D., Lane, T. E., & LaFerla, F. M. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.02.012 · Cited by 210 · 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 · cited 1× · see citing works
“A similar sample size in another tau immunotherapy study was found to be suitable to detect significant differences for the Y-maze task as well (Troquier et al., 2012).”
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 · cited 1× · see citing works
“Because tau is an endogenous protein with normal cellular functions, such treatments carry the risk of inducing autoimmunity and/or other related complications (Rosenmann et al., 2006).”
BackgroundEfficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice
Boimel, M., Grigoriadis, N., Lourbopoulos, A., Haber, E., Abramsky, O., & Rosenmann, H. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.05.010 · Cited by 174 · cited 2× · 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…”
BackgroundBi, M., Ittner, A., Ke, Y. D., Götz, J., & Ittner, L. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026860 · Cited by 153 · cited 4× · see citing works
“The JNPL3 mouse model (Lewis et al., 2000) expresses a frontotemporal dementia-associated human mutant tau transgene (P301L) and has been used previously for tau immunotherapy (Asuni et al., 2007; Chai et al., 2011; Bi et al., 2011).”
BackgroundMethodInfluentialRapid Accumulation of Endogenous Tau Oligomers in a Rat Model of Traumatic Brain Injury
Hawkins, B. E., Krishnamurthy, S., Castillo‐Carranza, D. L., Sengupta, U., Prough, D. S., Jackson, G. R., DeWitt, D. S., & Kayed, R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.472746 · Cited by 148 · cited 2× · see citing works
“, tau oligomeric intermediates) in tauopathies is poorly understood; however, novel polyclonal and monoclonal antibodies that define specific tau species have enabled the study of tau oligomers in vivo (Patterson et al., 2011; Lasagna-Reeves et al., 2012a; Blair et al., 2013; Hawkins et al., 2013; Wu et al., 2013).”
BackgroundSelf-citationTau 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
Tau-Based Treatment Strategies in Neurodegenerative Diseases
Schneider, A., & Mandelkow�, E. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2008.05.006 · Cited by 142 · cited 1× · see citing works
“…(Ballatore et al., 2007; Haroutunian et al., 2007) and amyloid- (A )- mediated neurotoxicity (Rapoport et al., 2002; Roberson et al., 2007), tau-based therapeutic approaches have lagged behind those targeting A (Schneider and Mandelkow, 2008; LasagnaReeves et al., 2011b; Ubhi and Masliah, 2011).”
BackgroundLemere, C. A. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(03)00044-5 · Cited by 138 · cited 1× · see citing works
“The mechanism of tau oligomer clearance appears to occur via a peripheral pathway similar to several previously described for the clearance of other amyloid proteins (DeMattos et al., 2001; Lemere et al., 2003; Oddo et al., 2004; Masliah et al., 2005; Winkler et al., 2010).”
Formation and Propagation of Tau Oligomeric Seeds
Gerson, J. E., & Kayed, R. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00093 · Cited by 137 · see citing works
Self-citationAmyloid-β Annular Protofibrils Evade Fibrillar Fate in Alzheimer Disease Brain
Lasagna‐Reeves, C. A., Glabe, C. G., & Kayed, R. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.236257 · Cited by 136 · see citing works
Self-citationThakker, D. R., Weatherspoon, M. R., Harrison, J., Keene, T. E., Lane, D. S., Kaemmerer, W. F., Stewart, G. R., & Shafer, L. L. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813404106 · Cited by 124 · cited 2× · see citing works
“…phenotypes and specifically clears tau oligomers in P301L mice Injection of anti-amyloid antibodies in AD animal models via intracerebroventricular injection has been performed in a few well executed studies (Chauhan and Siegel, 2003; Oddo et al., 2004; Chauhan, 2007; Thakker et al., 2009).”
MethodYamada, K., Yabuki, C., Seubert, P., Schenk, D., Hori, Y., Ohtsuki, S., Terasaki, T., Hashimoto, T., & Iwatsubo, T. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.2021-09.2009 · Cited by 117 · see citing works
Immunotherapy Targeting Pathological Tau Protein in Alzheimer's Disease and Related Tauopathies
Sigurdsson, E. M. (2008) · Journal of Alzheimer's Disease · doi:10.3233/jad-2008-15202 · Cited by 116 · cited 2× · see citing works
“…exclusive and it has been demonstrated that different clearance mechanisms can be activated to different degrees depending on the antibody and its target (DeMattos et al., 2001; Levites et al., 2006; Sigurdsson, 2008; Golde et al., 2009; Masliah et al., 2011; Morgan, 2011; Ubhi and Masliah, 2011).”
BackgroundInsights into the mechanisms of action of anti‐Aβ antibodies in Alzheimer's disease mouse models
Levites, Y., Smithson, L. A., Price, R. W., Dakin, R. S., Yuan, B., Sierks, M. R., Kim, J., McGowan, E., Kim Reed, D., Rosenberry, T. L., et al. (2006) · The FASEB Journal · doi:10.1096/fj.06-6463fje · Cited by 113 · see citing works
Are Tangles as Toxic as They Look?
Spires‐Jones, T. L., Kopeikina, K. J., Koffie, R. M., de Calignon, A., & Hyman, B. T. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-011-9566-7 · Cited by 110 · cited 1× · see citing works
“…metastable tau aggregates such as NFTs are not causally linked to tauopathy phenotypes in animal models (Wittmann et al., 2001; Santacruz et al., 2005; Berger et al., 2007; Yoshiyama et al., 2007; Polydoro et al., 2009; LasagnaReeves et al., 2011b; Spires-Jones et al., 2011; Cowan et al., 2012).”
BackgroundFox, L. M., William, C. M., Adamowicz, D. H., Pitstick, R., Carlson, G. A., Spires-Jones, T. L., & Hyman, B. T. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318220a658 · Cited by 88 · cited 1× · see citing works
“In addition, environmental enrichment reduced soluble tau and restored Arc messenger RNA levels in rTg4510-transgenic mice overexpressing P301L mutant human tau protein despite the continued presence of NFT pathology (Fox et al., 2011).”
BackgroundTau protein abnormalities associated with the progression of alzheimer disease type dementia
Haroutunian, V., Davies, P., Vianna, C., Buxbaum, J. D., & Purohit, D. P. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.11.001 · Cited by 86 · see citing works
Tau Oligomers as Potential Targets for Immunotherapy for Alzheimers Disease and Tauopathies
A. Lasagna-Reeves, C., L. Castillo-Carranza, D., R. Jackson, G., & Kayed, R. (2011) · Current Alzheimer Research · doi:10.2174/156720511796717177 · Cited by 80 · cited 2× · see citing works
“The supernatants were aliquoted, snap-frozen, and stored at 80°C until use (Lasagna-Reeves et al., 2011a).”
BackgroundMethodSelf-citationKrishnamurthy, P., Deng, Y., & Sigurdsson, E. M. (2011) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2011.00059 · Cited by 71 · cited 2× · see citing works
“The supernatants were aliquoted, snap-frozen, and stored at 80°C until use (Lasagna-Reeves et al., 2011a).”
BackgroundMethodExtensive p‐Tau Pathology and SDS‐Stable p‐Tau Oligomers in Alzheimer's Cortical Synapses
Henkins, K. M., Sokolow, S., Miller, C. A., Vinters, H. V., Poon, W. W., Cornwell, L. B., Saing, T., & Gylys, K. H. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2012.00598.x · Cited by 70 · cited 2× · see citing works
“Furthermore, widespread tau oligomers accumulate at the synapses (Henkins et al., 2012), impairing the ubiquitin-proteasome system (Tai et al.”
BackgroundTau Oligomers as Potential Targets for Alzheimer’s Diagnosis and Novel Drugs
Guzmán‐Martínez, L., Farias, G. A., & Maccioni, R. B. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00167 · Cited by 62 · cited 1× · see citing works
“In summary, our studies support the notion that tau oligomer immunization strategies may be beneficial for AD and other tauopathies (Guzmán-Martinez et al., 2013).”
BackgroundWhat is the pathological significance of tau oligomers?
Cowan, C. M., Quraishe, S., & Mudher, A. K. (2012) · Biochemical Society Transactions · doi:10.1042/bst20120135 · Cited by 62 · cited 3× · see citing works
“The therapeutic effects of the TOMA antibody in P301L results in a reduction of pathogenic tau oligomers coinciding with the rescue of tauopathy-related motor and cognitive phenotypes in mice, reinforcing the concept that oligomers are the pathological form of tau in animal models of neurodegenerative tauopathy (Lasag…”
BackgroundDo neuronal inclusions kill the cell?
Terry, R. (2000) · Springer eBooks · doi:10.1007/978-3-7091-6781-6_12 · Cited by 48 · cited 1× · see citing works
“…NFT-containing neurons can survive for decades (Morsch et al., 1999) and neuronal loss precedes or is independent of NFT formation (Gómez-Isla et al., 1997; Terry, 2000; Maeda et al., 2006; van de Nes et al., 2008), suggesting that other tau species may contribute to earlier stages of disease.”
BackgroundApparent Behavioral Benefits of Tau Overexpression in P301L Tau Transgenic Mice
Morgan, D., Munireddy, S., Alamed, J., DeLeon, J., Diamond, D. M., Bickford, P. C., Hutton, M. L., Lewis, J. M., McGowan, E. M., & Gordon, M. N. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-15407 · Cited by 46 · cited 1× · see citing works
“To determine the effect of immunotherapy on behavioral deficits, the spatial memory and motor function of P301L and wildtype mice were evaluated by rotarod and Y-maze tests (Holcomb et al., 1999; Morgan et al., 2008).”
MethodQuantitative and Mechanistic Studies of A&#946; Immunotherapy
Golde, T., Das, P., & Levites, Y. (2009) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152709787601830 · Cited by 46 · see citing works
Intracerebroventricular passive immunization with anti‐Aβ antibody in Tg2576
Chauhan, N. B., & Siegel, G. J. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10721 · Cited by 45 · cited 2× · see citing works
“…phenotypes and specifically clears tau oligomers in P301L mice Injection of anti-amyloid antibodies in AD animal models via intracerebroventricular injection has been performed in a few well executed studies (Chauhan and Siegel, 2003; Oddo et al., 2004; Chauhan, 2007; Thakker et al., 2009).”
Methodvan de Nes, J. A. P., Nafe, R., & Schlote, W. (2008) · Brain Research · doi:10.1016/j.brainres.2008.03.043 · Cited by 40 · see citing works
Gu, J., & Sigurdsson, E. M. (2011) · Journal of Molecular Neuroscience · doi:10.1007/s12031-011-9576-5 · Cited by 34 · cited 2× · see citing works
“…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 in animal models.”
BackgroundTau aggregates as immunotherapeutic targets.
Castillo-Carranza, D. L., Lasagna-Reeves, C., & Kayed, R. (2013) · Frontiers in Bioscience · doi:10.2741/s381 · Cited by 33 · see citing works
Self-citationIntracerebroventricular passive immunization with anti‐oligoAβ antibody in TgCRND8
Chauhan, N. B. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21110 · Cited by 24 · cited 2× · see citing works
“…phenotypes and specifically clears tau oligomers in P301L mice Injection of anti-amyloid antibodies in AD animal models via intracerebroventricular injection has been performed in a few well executed studies (Chauhan and Siegel, 2003; Oddo et al., 2004; Chauhan, 2007; Thakker et al., 2009).”
MethodRecent advances in the development of immunotherapies for tauopathies
Ubhi, K. K., & Masliah, E. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.10.007 · Cited by 15 · cited 7× · see citing works
“…exclusive and it has been demonstrated that different clearance mechanisms can be activated to different degrees depending on the antibody and its target (DeMattos et al., 2001; Levites et al., 2006; Sigurdsson, 2008; Golde et al., 2009; Masliah et al., 2011; Morgan, 2011; Ubhi and Masliah, 2011).”
BackgroundInfluentialImmunotherapy for the treatment of Alzheimer's disease: amyloid-β or tau, which is the right target?
Kayed, R., Castillo‐Carranza, D. L., & Guerrero‐Munoz, M. J. (2013) · ImmunoTargets and Therapy · doi:10.2147/itt.s40131 · Cited by 15 · see citing works
Self-citationWinkler, D. T., Abramowski, D., Danner, S., Zurini, M. G. M., Paganetti, P., Tolnay, M., & Staufenbiel, M. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.01.030 · Cited by 14 · see citing works
Gallyas, F. (2008) · Biotechnic & Histochemistry · doi:10.1080/10520290802538543 · Cited by 13 · see citing works
Flagged first, then by citations
1 of the 76 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251 · see citing works
Clearance systems in the brain—implications for Alzheimer disease
Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., et al. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.119 · Cited by 1,678 · see citing works
Depletion of microglia and inhibition of exosome synthesis halt tau propagation
Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., Wolozin, B., Butovsky, O., Kügler, S., & Ikezu, T. (2015) · Nature Neuroscience · doi:10.1038/nn.4132 · Cited by 1,591 · see citing works
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
Tau and neurodegenerative disease: the story so far
Iqbal, K., Liu, F., & Gong, C.-X. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.225 · Cited by 806 · see citing works
The release and trans-synaptic transmission of Tau via exosomes
Wang, Y., Balaji, V., Kaniyappan, S., Krüger, L., Irsen, S., Tepper, K., Chandupatla, R., Maetzler, W., Schneider, A., Mandelkow, E., et al. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0143-y · Cited by 674 · see citing works
Half a century of amyloids: past, present and future
Ke, P. C., Zhou, R., Serpell, L. C., Riek, R., Knowles, T. P. J., Lashuel, H. A., Gazit, E., Hamley, I. W., Davis, T. P., Fändrich, M., et al. (2020) · Chemical Society Reviews · doi:10.1039/c9cs00199a · Cited by 567 · 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
α-Synuclein misfolding and aggregation: Implications in Parkinson’s disease pathogenesis
Mehra, S., Sahay, S., & Maji, S. K. (2019) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2019.03.001 · Cited by 507 · see citing works
Tau impairs neural circuits, dominating amyloid-β effects, in Alzheimer models in vivo
Busche, M. A., Wegmann, S., Dujardin, S., Commins, C., Schiantarelli, J., Klickstein, N., Kamath, T. V., Carlson, G. A., Nelken, I., & Hyman, B. T. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0289-8 · Cited by 413 · see citing works
Targeting protein aggregation for the treatment of degenerative diseases
Eisele, Y. S., Monteiro, C., Fearns, C., Encalada, S. E., Wiseman, R. L., Powers, E. T., & Kelly, J. W. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4593 · Cited by 416 · see citing works
Amyloid-β and tau complexity — towards improved biomarkers and targeted therapies
Polanco, J. C., Li, C., Bodea, L., Martínez‐Mármol, R., Meunier, F. A., & Götz, J. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.162 · Cited by 374 · see citing works
Tau Aggregation and Its Interplay with Amyloid-β
Nisbet, R. M., Polanco, J.-C., Ittner, L. M., & Götz, J. (2015) · Acta Neuropathologica · doi:10.1007/s00401-014-1371-2 · Cited by 359 · see citing works
“Just days after the injections, immunized mice exhibited improved cognitive performance and motor activity, and a significant reduction in oligomeric tau levels in the brain and spinal cord [18].”
BackgroundTau-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
“Antibody treat-ment can increase serum tau levels, which might indicate removal from the brain via Fc receptors or, more likely, an increased half-life of antibody-bound tau 187–189 .”
BackgroundTau Oligomers: Cytotoxicity, Propagation, and Mitochondrial Damage
Shafiei, S. S., Guerrero-Muñoz, M. J., & Castillo-Carranza, D. L. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00083 · Cited by 314 · see citing works
“When tau oligomers, rather than tau monomers or fibrils, are injected into the brain of wild-type mice, cognitive, synaptic, and mitochondrial abnormalities follow (LasagnaReeves et al., 2011; Castillo-Carranza et al., 2014b).”
BackgroundSelf-citationA 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
Chen, X., & Mobley, W. C. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00659 · Cited by 291 · see citing works
“In vivo, using the hippocampal cognitive test just referenced, intravenous TOMA injection was shown to block the effect of intracerebroventricular (ICV) injection of AD brain-derived tau oligomers, an effect that was correlated with reduced levels of tau oligomers in the injected mouse brain (Castillo-Carranza et al.,…”
MethodSynaptic 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
“This therapy has been shown both in vitro and in vivo to be successful at preventing both tau pathology formation and propagation (Boimel et al., 2010; Bi et al., 2011; Yanamandra et al., 2013; Castillo-Carranza et al., 2014; Ittner et al., 2015; Nicholls et al., 2017; Nobuhara et al., 2017).”
BackgroundMechanisms of Cell-to-Cell Transmission of Pathological Tau: A Review
Gibbons, G. S., Lee, V. M. Y., & Trojanowski, J. Q. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.2505 · Cited by 257 · 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
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
Ectosomes: A New Mechanism for Non-Exosomal Secretion of Tau Protein
Dujardin, S., Bégard, S., Caillierez, R., Lachaud, C., Delattre, L., Carrier, S., Loyens, A., Galas, M., Bousset, L., Melki, R., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100760 · Cited by 215 · see citing works
“Nevertheless, a recent study of Kayed’s group demonstrated that passive immunization with Tau oligomer monoclonal antibody reverses tauopathy phenotypes [64].”
BackgroundIntersection 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
“↓ P-tau, ↓insoluble tau, NC survival, NC micro- and astrogliosis Castillo-Carranza (2014) [53] TOMA (conformational) JPNL3 8M Single injection (30ug/mouse i.v. & 1ug/mouse i.c.v) ↓Tau oligomers, NC microgliosis and cytokines, improved cognition & motor deficits Castillo-Carranza (2014) [50] TOMA…”
BackgroundCollin, L., Bohrmann, B., Göpfert, U., Oroszlan‐Szovik, K., Ozmen, L., & Grüninger, F. (2014) · Brain · doi:10.1093/brain/awu213 · Cited by 203 · see citing works
“Several passive immunization studies in mice provide a strong rationale for developing tau immunotherapy for Alzheimer’s dis- ease (Boutajangout et al., 2011; Chai et al., 2011; d’Abramo et al., 2013; Castillo-Carranza et al., 2014).”
BackgroundInfluentialWobst, H. J., Sharma, A. M., Diamond, M. I., Wanker, E. E., & Bieschke, J. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.11.026 · Cited by 202 · see citing works
Tau Assembly: The Dominant Role of PHF6 (VQIVYK) in Microtubule Binding Region Repeat R3
Ganguly, P., Do, T. D., Larini, L., LaPointe, N. E., Sercel, A. J., Shade, M. F., Feinstein, S. C., Bowers, M. T., & Shea, J. (2015) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.5b00175 · Cited by 191 · 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
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
“This type of mechanism was suggested by a recent study.(21) While there is as yet no direct evidence for this possibility, if future methods allow for detection of extracellular species of tau oligomers in vivo, this hypothesis may be testable.”
BackgroundNisbet, R. M., Van der Jeugd, A., Leinenga, G., Evans, H. T., Janowicz, P. W., & Götz, J. (2017) · Brain · doi:10.1093/brain/awx052 · Cited by 187 · see citing works
“Furthermore, immunization with anti-tau antibodies has proven efficacious in multiple preclinical models (Boutajangout et al., 2011; Yanamandra et al., 2013; Castillo-Carranza et al., 2014; Ittner et al., 2015).”
Prevention of tau seeding and propagation by immunotherapy with a central tau epitope antibody
Albert, M., Mairet‐Coello, G., Danis, C., Lieger, S., Caillierez, R., Carrier, S., Skrobala, E., Landrieu, I., Michel, A., Schmitt, M., et al. (2019) · Brain · doi:10.1093/brain/awz100 · Cited by 177 · see citing works
Targeting Amyloid Aggregation: An Overview of Strategies and Mechanisms
Giorgetti, S., Greco, C., Tortora, P., & Aprile, F. A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092677 · Cited by 174 · see citing works
“For example, camel single domain antibodies, generally referred as nanobodies, are extremely effective inhibitors of the aggregation of several amyloidogenic proteins, including lysozyme [63], α-synuclein (α-syn) [64], Aβ [65], tau [101], and β2-m [66].”
BackgroundTau 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
Nilson, A. N., English, K. C., Gerson, J. E., Whittle, T. B., Crain, C. N., Xue, J. J., Sengupta, U., Castillo‐Carranza, D. L., Zhang, W., Gupta, P. K., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160912 · Cited by 170 · see citing works
Self-citationKanmert, 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
“…released passively as a result of cell death or via active processes, the therapeutic use of antibodies that target aggregated tau or MTBR-containing aggregationcompetent forms of tau appear to offer great promise (Gu and Sigurdsson, 2011; Castillo-Carranza et al., 2014; Holmes and Diamond, 2014).”
BackgroundAmyloidogenesis of Tau protein
Niżyński, B., Dzwolak, W., & Nieznański, K. (2017) · Protein Science · doi:10.1002/pro.3275 · Cited by 157 · see citing works
Ghag, G., Bhatt, N. N., Cantu, D. V., Guerrero‐Munoz, M. J., Ellsworth, A., Sengupta, U., & Kayed, R. (2018) · Protein Science · doi:10.1002/pro.3499 · Cited by 157 · see citing works
Self-citationPassive 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
“A tau oligomer-selective monoclonal antibody (TOMA) was developed by Kayed and colleagues (Castillo-Carranza et al. (2014)), by immunizing BALB/c mice with recombinant (―synthetic‖) tau oligomers. TOMA is a murine IgG1 that selectively recognizes tau oligomers over either monomeric tau or tau NFTs. Its epitope has not…”
InfluentialCastillo-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
“Recently, we demonstrated that reduction of tau oligomers through passive immunization reversed cognitive and motor deficits associated with tau pathology in mice (Castillo-Carranza et al., 2014a,b).”
BackgroundMethodSelf-citationMotor and cognitive deficits in aged tau knockout mice in two background strains
Lei, P., Ayton, S., Moon, S., Zhang, Q., Volitakis, I., Finkelstein, D. I., & Bush, A. I. (2014) · Molecular Neurodegeneration · doi:10.1186/1750-1326-9-29 · Cited by 145 · see citing works
“reducing tau can ameliorate Aβ-induced toxicity [11,15,49,50] and rescue the toxicity in mouse mutant tau transgenic models [51-54].”
Stancu, I.-C., Vasconcelos, B., Ris, L., Wang, P., Villers, A., Peeraer, E., Buist, A., Terwel, D., Baatsen, P., Oyelami, T., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1413-4 · Cited by 143 · see citing works
“These data are in line with clear demonstration of detrimental effects of Tau-oligomers on neuronal function and behavior, as demonstrated following acute injection of oligomeric Tau and immunization with anti-Tau oligomeric antibodies [10, 11, 39, 40].”
ResultTherapy and clinical trials in frontotemporal dementia: past, present, and future
Tsai, R. M., & Boxer, A. L. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13640 · Cited by 145 · see citing works
Derry, P. J., Hegde, M. L., Jackson, G. R., Kayed, R., Tour, J. M., Tsai, A.-L., & Kent, T. A. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101716 · Cited by 142 · see citing works
“Passive immunization with TOMA against NFTs was not seen and TOMA was not observed to enter the cellular compartment suggesting a strictly extracellular role of the antibody (Castillo-Carranza et al., 2014).”
BackgroundSelf-citationThe role of tau in the pathological process and clinical expression of Huntington’s disease
Vuono, R., Winder‐Rhodes, S., de Silva, R., Cisbani, G., Drouin‐Ouellet, J., REGISTRY Investigators of the European Huntington’s Disease Network, Spillantini, M. G., Cicchetti, F., & Barker, R. A. (2015) · Brain · doi:10.1093/brain/awv107 · Cited by 139 · 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
“These efforts have resulted in the generation of the TOC1 (Patterson et al., 2011), TOMA (Castillo-Carranza et al., 2014), and T22 (LasagnaReeves et al., 2012) antibodies that recognize intermediate tau aggregates.”
Niewiadomska, G., Niewiadomski, W., Steczkowska, M., & Gąsiorowska, A. (2021) · Life · doi:10.3390/life11010028 · Cited by 132 · 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
Phagocytosis of full-length Tau oligomers by Actin-remodeling of activated microglia
Das, R. R., Balmik, A. A., & Chinnathambi, S. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1694-y · Cited by 129 · 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
“Various tau antibodies directed against distinct epitopes have been tested, including N-terminal antibodies,(9,10) phospho-tauespecific antibodies, and conformation-dependent antibodies.(12,16) Some of these antibodies appear to ameliorate the cognitive impairments as well as the neuropathology of tau-transgenic mice;…”
BackgroundCerebral Microvascular Accumulation of Tau Oligomers in Alzheimer’s Disease and Related Tauopathies
Castillo-Carranza, D. L., Nilson, A. N., Van Skike, C. E., Jahrling, J. B., Patel, K., Garach, P., Gerson, J. E., Sengupta, U., Abisambra, J., Nelson, P., et al. (2017) · Aging and disease · doi:10.14336/ad.2017.0112 · Cited by 118 · see citing works
“Recently we demonstrated that specific removal of tau oligomers through passive immunotherapy using a tau oligomer-specific monoclonal antibody improves cognitive function without disrupting large NFTs in several tauopathy mouse models including the Tg2576, P301L, and Htau mice [38-41].”
BackgroundSelf-citationInsulin resistance in Alzheimer's disease
Dineley, K. T., Jahrling, J. B., & Denner, L. A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.09.001 · Cited by 124 · see citing works
Self-citationThe Role of Tau Oligomers in the Onset of Alzheimer's Disease Neuropathology
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
Wang, P., Joberty, G., Buist, A., Vanoosthuyse, A., Stancu, I., Vasconcelos, B., Pierrot, N., Faelth-Savitski, M., Kienlen‐Campard, P., Octave, J., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1663-9 · Cited by 118 · see citing works
“The detrimental role of Tau oligomers in neuronal function and behavior was further demonstrated using acute injection of oligomeric Tau and immunization with anti-Tau oligomeric antibodies [11, 12, 39, 40].”
BackgroundGaikwad, S., Senapati, S., Haque, M. A., & Kayed, R. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13490 · Cited by 117 · see citing works
Self-citationRecent therapeutic strategies targeting beta amyloid and tauopathies in Alzheimer's disease
Madav, Y., Wairkar, S., & Prabhakar, B. R. (2019) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2019.01.004 · Cited by 116 · see citing works
Kulenkampff, K., Perez, A.-M. W., Sormanni, P., Habchi, J., & Vendruscolo, M. (2021) · Nature Reviews Chemistry · doi:10.1038/s41570-021-00254-9 · Cited by 110 · see citing works
Immunotherapies for Neurodegenerative Diseases
Mortada, I., Farah, R., Nabha, S. M., Ojcius, D. M., Fares, Y., Almawi, W. Y., & Sadier, N. S. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.654739 · Cited by 112 · see citing works
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
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
“cits in a mouse model of tauopathy [39].”
BackgroundTau-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
Pathological Changes of Tau Related to Alzheimer’s Disease
Chu, D., & Liu, F. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00457 · Cited by 103 · see citing works
Anti-tau antibody administration increases plasma tau in transgenic mice and patients with tauopathy
Yanamandra, K., Patel, T. K., Jiang, H., Schindler, S., Ulrich, J. D., Boxer, A. L., Miller, B. L., Kerwin, D. R., Gallardo, G., Stewart, F., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aal2029 · Cited by 100 · see citing works
“First, whether all antitau antibodies will increase plasma tau as we report here is not yet known, although others have also observed increases in serum tau after administration of different anti-tau antibodies to tau Tg mice (16, 42).”
BackgroundErcan-Herbst, E., Ehrig, J., Schöndorf, D. C., Behrendt, A., Klaus, B., Gomez Ramos, B., Prat Oriol, N., Weber, C., & Ehrnhoefer, D. E. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0823-2 · Cited by 101 · see citing works
“To analyze different tau structures, conformationspecific antibodies have been developed, which are thought to react with the different folding states of the protein: Antibodies raised against oligomeric forms of tau such as T22, TOC1 and TOMA selectively label tau oligomers over monomers [24, 25, 32], whereas Alz50 a…”
BackgroundRao, M. V., McBrayer, M. K., Campbell, J., Kumar, A., Hashim, A. T., Sershen, H. W., Stavrides, P. H., Ohno, M., Hutton, M., & Nixon, R. A. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1132-14.2014 · Cited by 99 · see citing works
“Multiple antibodies, including Tau-5, T22, AT8, tau oligomer complex 1 (TOC1), and tau oligomer-specific monoclonal antibodies (TOMAs), have been used to detect tau species in the range of 100 –170 kDa, which have been termed tau multimers, oligomers, or highmolecular-weight tau-immunoreactive bands by different inves…”
BackgroundInfluentialTau forms oligomeric complexes on microtubules that are distinct from tau aggregates
Gyparaki, M. T., Arab, A., Sorokina, E. M., Santiago-Ruiz, A. N., Bohrer, C. H., Xiao, J., & Lakadamyali, M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2021461118 · Cited by 96 · see citing works
“Moreover, injection of tau oligomers rather than monomers or fibrils into the brain of wild-type mice was sufficient to produce cognitive and synaptic abnormalities (15, 16).”
BackgroundCurrent 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
Shulman, M. B., Kong, J., O'Gorman, J. T., Ratti, E., Rajagovindan, R., Viollet, L., Huang, E., Sharma, S., Racine, A. M., Czerkowicz, J., et al. (2023) · Nature Aging · doi:10.1038/s43587-023-00523-w · Cited by 100 · see citing works
Characterization of tau oligomeric seeds in progressive supranuclear palsy
Gerson, J. E., Sengupta, U., Lasagna‐Reeves, C. A., Guerrero‐Munoz, M. J., Troncoso, J. C., & Kayed, R. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-73 · Cited by 95 · see citing works
“These results combined with recent studies showing the efficacy of passive immunotherapy targeting tau oligomers [44,45] support the possibility of utilizing this strategy for therapeutics in PSP, as well as in other neurodegenerative tauopathies.”
ResultSelf-citationDai, 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
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
Dujardin, S., Colin, M., & Buée, L. (2014) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12200 · Cited by 88 · see citing works
Hussong, S. A., Banh, A. Q., Skike, C. E. V., Dorigatti, A. O., Hernandez, S. F., Hart, M. J., Ferrán, B., Makhlouf, H., Gaczynska, M. E., Osmulski, P. A., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-37840-y · Cited by 82 · see citing works
“Thus, whether the restoration of micro-vascular function by TOMA is driven by the removal of soluble tau aggregates from microvascular endothelial cells alone, or in combination with the removal of pathogenic tau from other brain cell types or potentially from cell types of the periphery cannot be ascertained from our…”
InfluentialSelf-citationTau‐targeting passive immunization modulates aspects of pathology in tau transgenic mice
Ittner, A., Bertz, J., Suh, L. S., Stevens, C. H., Götz, J., & Ittner, L. M. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12821 · Cited by 81 · see citing works
Is Huntington's disease a tauopathy?
Gratuze, M., Cisbani, G., Cicchetti, F., & Planel, E. (2016) · Brain · doi:10.1093/brain/aww021 · Cited by 81 · see citing works
Tau oligomers mediate α-synuclein toxicity and can be targeted by immunotherapy
Gerson, J. E., Farmer, K. M., Henson, N., Castillo‐Carranza, D. L., Murillo, M. C., Sengupta, U., Barrett, A. D. T., & Kayed, R. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0245-9 · Cited by 79 · see citing works
Self-citationRegulation of neuronal microtubule dynamics by tau: Implications for tauopathies
Venkatramani, A., & Panda, D. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.04.120 · Cited by 79 · see citing works
Tau oligomers in cerebrospinal fluid in Alzheimer's disease
Sengupta, U., Portelius, E., Hansson, O., Farmer, K., Castillo‐Carranza, D., Woltjer, R., Zetterberg, H., Galasko, D., Blennow, K., & Kayed, R. (2017) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.382 · Cited by 77 · see citing works
Self-citationSigurdsson, E. M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179937 · Cited by 76 · see citing works
“These include non-phosphorylated- [27,30,32,41,42,46–48,69,70], phosphorylated[20,24,25,27,29,35,39,43,49], conformational-/oligomeric [20,31,33,34,40,44,45], and a truncated epitope [66,71].”
The Role of Post-Translational Modifications on the Structure and Function of Tau Protein
Ye, H., Han, Y., Li, P., Su, Z., & Huang, Y. (2022) · Journal of Molecular Neuroscience · doi:10.1007/s12031-022-02002-0 · Cited by 74 · see citing works
“While the detailed conformations of tau oligomers remain unknown, they should be different from those of tau monomer and the hydrophobic segments in the MTBD may become more exposed (Castillo-Carranza et al. 2014; Lasagna-Reeves et al. 2010, 2012; Maeda et al. 2007; Mirbaha et al. 2018; Patterson et al. 2011).”
BackgroundPassive immunotherapy of tauopathy targeting pSer413‐tau: a pilot study in mice
Umeda, T., Eguchi, H., Kunori, Y., Matsumoto, Y., Taniguchi, T., Mori, H., & Tomiyama, T. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.171 · Cited by 73 · see citing works
“The clearance of extracellular tau by passive immunization may shift the equilibrium between the extracellular and intracellular tau pools, leading to the removal of intracellular tau.(37) Another plausible mechanism to the clearance of pathological tau could be lysosomes absorbing tau aggregates in the cytoplasm (via…”
BackgroundInfluentialLu, K. P., Kondo, A., Albayram, Ö., Herbert, M. K., Liu, H., & Zhou, X. Z. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.2027 · Cited by 74 · see citing works
Potential mechanisms and implications for the formation of tau oligomeric strains
Gerson, J. E., Mudher, A. K., & Kayed, R. (2016) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.1080/10409238.2016.1226251 · Cited by 74 · see citing works
Self-citationGerson, J. E., Castillo‐Carranza, D. L., & Kayed, R. (2014) · ACS Chemical Neuroscience · doi:10.1021/cn500143n · Cited by 73 · see citing works
Self-citationThe interrelationship of proteasome impairment and oligomeric intermediates in neurodegeneration
Deger, J. M., Gerson, J. E., & Kayed, R. (2015) · Aging Cell · doi:10.1111/acel.12359 · Cited by 69 · see citing works
“Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. in disease progression and validate tau oligomers as a potential drug target (Castillo-Carranza et al., 2013, 2014a,b).”
BackgroundSelf-citationToxic Tau Oligomers Modulated by Novel Curcumin Derivatives
Cascio, F. L., Puangmalai, N., Ellsworth, A., Bucchieri, F., Pace, A., Piccionello, A. P., & Kayed, R. (2019) · Scientific Reports · doi:10.1038/s41598-019-55419-w · Cited by 71 · see citing works
Self-citationPuangmalai, N., Sengupta, U., Bhatt, N., Gaikwad, S., Montalbano, M., Bhuyan, A., Garcia, S., McAllen, S., Sonawane, M., Jerez, C., et al. (2022) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.101766 · Cited by 68 · see citing works
“Soluble tau oligomers have been identified as the more toxic species and most relevant to disease progression (8, 13).”
BackgroundSelf-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
Amyloid-β oligomers as a template for secondary amyloidosis in Alzheimer's disease
Guerrero‐Munoz, M. J., Castillo‐Carranza, D. L., Krishnamurthy, S., Paulucci-Holthauzen, A. A., Sengupta, U., Lasagna‐Reeves, C. A., Ahmad, Y., Jackson, G. R., & Kayed, R. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.08.008 · Cited by 67 · see citing works
Self-citationViolet, M., Chauderlier, A., Delattre, L., Tardivel, M., Chouala, M. S., Sultan, A., Marciniak, E., Humez, S., Binder, L. I., Kayed, R., et al. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.09.003 · Cited by 66 · see citing works
Self-citationTargeting tau in Alzheimer's disease: from mechanisms to clinical therapy
Ye, J., Wan, H., Chen, S., & Liu, G. (2023) · Neural Regeneration Research · doi:10.4103/1673-5374.385847 · Cited by 69 · see citing works
“…(Asuni et al., 2007; Liu et al., 2016), p-Ser413 (Umeda et al., 2015), p-Ser422 (Collin et al., 2014; van Ameijde et al., 2018)), oligomeric tau (Castillo-Carranza et al., 2014; Bittar et al., 2022), fragmented tau (Dam et al., 2021), N-terminal tau (Dai et al., 2018), and total tau (Höglinger…”
Antibody-DerivedIn VivoImaging of Tau Pathology
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
The Enigma of Tau Protein Aggregation: Mechanistic Insights and Future Challenges
Zheng, H., Sun, H., Cai, Q., & Tai, H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094969 · Cited by 65 · see citing works
“T22 (rabbit polyclonal) [179] and TOMA (mouse monoclonal) [180] were generated against oligomeric-A β -induced tau trimers.”
BackgroundAgadjanyan, M. G., Petrovsky, N., & Ghochikyan, A. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.06.1884 · Cited by 65 · see citing works
“Remarkably, a single intravenous injection of Mab cleared oligomeric tau, rescued the locomotor phenotype, and reversed the memory deficits associated with oligomeric tau pathology [154].”
BackgroundCongdon, E. E., Lin, Y., Rajamohamedsait, H. B., Shamir, D. B., Krishnaswamy, S., Rajamohamedsait, W. J., Rasool, S., González‐Calle, V., Levenga, J., Gu, J., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0126-z · Cited by 63 · see citing works
“However, some antibodies do not appear to be taken up in appreciable amounts and are likely to primarily work extracellularly [15–17].”
BackgroundTau-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
Kayed, R., Dettmer, U., & Lesné, S. (2020) · Journal of Parkinson s Disease · doi:10.3233/jpd-201965 · Cited by 62 · see citing works
“Based on the properties of TOMA antibodies, which preferentially detect off-pathway o-Tau [205], and based on those for F8H7 and Syn33, which preferentially bind off-pathway o- Syn [89], these findings highlight complex molecular interactions between oSyn and o-Tau, which are not fully clear at this time.”
BackgroundSelf-citationTau 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
“In addition, following a decrease in oligomeric tau levels, improved cognitive function suggests the potential of anti-tau antibody infusions as a therapeutic approach (214).”
BackgroundPatel, H., Martínez, P., Perkins, A., Taylor, X., Jury, N., McKinzie, D. L., & Lasagna‐Reeves, C. A. (2021) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2021.09.006 · Cited by 57 · see citing works
Self-citationPhysiological clearance of tau in the periphery and its therapeutic potential for tauopathies
Wang, J., Jin, W.-S., Bu, X.-L., Zeng, F., Huang, Z., Li, W.-W., Shen, L.-L., Zhuang, Z.-Q., Fang, Y.-Q., Sun, B.-L., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1891-2 · Cited by 61 · see citing works
Congdon, E. E., Chukwu, J. E., Shamir, D. B., Deng, J., Ujla, D., Sait, H. B. R., Neubert, T. A., Kong, X., & Sigurdsson, E. M. (2019) · EBioMedicine · doi:10.1016/j.ebiom.2019.03.033 · Cited by 55 · see citing works
Cox, K. K., Combs, B., Abdelmesih, B., Morfini, G., Brady, S., & Kanaan, N. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.07.015 · Cited by 54 · see citing works
“Indeed, multiple studies implicate oligomers as a primary toxic species of tau in several tauopathy model systems (Cardenas-Aguayo Mdel et al., 2014; Castillo-Carranza et al., 2014a; Fa et al., 2016; Gerson et al., 2016; Lewis and Dickson, 2016; Sahara et al., 2013; Tian et al., 2013; Usenovic et…”
Background
- Authors
- 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., & Kayed, R.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-03-19
- Volume
- 34
- Issue
- 12
- Pages
- 4260-4272
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6608097
- OpenAlex
- W1990986671
- Cited by
- 278
- References
- 76
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 15 · 2023: 21 · 2022: 13 · 2021: 20 · 2020: 30 · 2019: 25 · 2018: 34 · 2017: 27 · 2016: 21 · 2015: 28 · 2014: 23
- FWCI
- 21.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Drug Discovery Foundation
- 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
- tau oligomers, passive immunization, monoclonal antibodies, TOMAS, tauopathy, Alzheimer's disease, neurofibrillary tangles, hyperphosphorylated tau, locomotor deficits, memory impairment, antibody clearance, neurodegenerative disease treatment
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Immunization, Passive, Phosphorylation, Neurofibrillary Tangles, tau Proteins, Disease Progression, Tauopathies, Mice
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
