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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.
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“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
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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×
“…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×
“…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×
“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
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
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
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×
“…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×
“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
Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998
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Items 101–200 of 278
Vitale, F., Giliberto, L., Ruiz, S., Steslow, K., Marambaud, P., & d’Abramo, C. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0585-2 · Cited by 59
Highly specific and selective anti‐pS396‐tau antibody C10.2 targets seeding‐competent tau
Rosenqvist, N., Asuni, A. A., Andersson, C. R., Christensen, S., Daechsel, J. C. A., Egebjerg, J., Falsig, J., Helboe, L., Jul, P., Kartberg, F., et al. (2018) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.09.005 · Cited by 52
Qß Virus-like particle-based vaccine induces robust immunity and protects against tauopathy
Maphis, N. M., Peabody, J., Crossey, E., Jiang, S., Ahmad, F. A. J., Álvarez, M. J., Mansoor, S. K., Yaney, A., Yang, Y., Sillerud, L. O., et al. (2019) · npj Vaccines · doi:10.1038/s41541-019-0118-4 · Cited by 48
Antibody Therapeutics Targeting Aβ and TauPreprint
Gallardo, G., & Holtzman, D. M. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024331 · Cited by 55
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
“targeting different phospho-epitopes of tau [194] and by targeting tau oligomers [195].”
BackgroundRajamohamedsait, H., Rasool, S., Rajamohamedsait, W., Lin, Y., & Sigurdsson, E. M. (2017) · Scientific Reports · doi:10.1038/s41598-017-17313-1 · Cited by 49
Prospects for strain-specific immunotherapy in Alzheimer’s disease and tauopathies
Bittar, A., Sengupta, U., & Kayed, R. (2018) · npj Vaccines · doi:10.1038/s41541-018-0046-8 · Cited by 50
Self-citationSchroeder, S. K., Joly‐Amado, A., Gordon, M. N., & Morgan, D. (2015) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9637-6 · Cited by 51
Saroja, S. R., Sharma, A., Hof, P. R., & Pereira, A. C. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12518 · Cited by 45
Marciani, D. J. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13608 · Cited by 48
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
Gaikwad, S., Puangmalai, N., Sonawane, M., Montalbano, M., Price, R., Iyer, M. S., Ray, A., Moreno, S., & Kayed, R. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adj5958 · Cited by 46
“In this context, our previous studies indicated that a single dose of anti-tau antibody provides protection for a minimum of 2 months ( 112 ).”
MethodSelf-citationAlzheimer's disease vaccine development: A new strategy focusing on immune modulation
Marciani, D. J. (2015) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2015.08.008 · Cited by 45
“tau (Kayed, 2010; Castillo-Carranza et al., 2014).”
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 44
“While passive immunization and active immunization reduced tau phosphorylation and oligomerization in tau transgenic animal models [7, 8, 16], it is unknown whether tau immunotherapy has an effect on tau pathology in human brain.”
The prion-like transmission of tau oligomers via exosomes
Jackson, N. A., Guerrero‐Munoz, M. J., & Castillo‐Carranza, D. L. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.974414 · Cited by 46
Self-citationLuciani, M., Montalbano, M., Troncone, L., Bacchin, C., Uchida, K., Daniele, G., Wolf, B. J., Butler, H. M., Kiel, J., Berto, S., et al. (2023) · European Heart Journal · doi:10.1093/eurheartj/ehad205 · Cited by 43
Self-citationRecent developments with tau-based drug discovery
Iqbal, K., Liu, F., & Gong, C. (2018) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2018.1445084 · Cited by 46
Tau Oligomers as Pathogenic Seeds: Preparation and Propagation In Vitro and In Vivo
Gerson, J. E., Sengupta, U., & Kayed, R. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6598-4_9 · Cited by 43
“Antibody Antibody 1 T22 [24] Antibody 2 Tau oligomer-specific monoclonal antibody (TOMA-1) [22]”
BackgroundSelf-citationVaccination strategies in tauopathies and synucleinopathies
Braczynski, A. K., Schulz, J. B., & Bach, J. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14207 · Cited by 44
Gibbons, G. S., Kim, S., Wu, Q., Riddle, D. M., Leight, S. N., Changolkar, L. N., Xu, H. W., Meymand, E. S., O’Reilly, M., Zhang, B., et al. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00404-5 · Cited by 45
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 42
The structure and phase of tau: from monomer to amyloid filament
Zeng, Y., Yang, J., Zhang, B., Gao, M., Su, Z., & Huang, Y. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03681-x · Cited by 45
Selenica, M.-L. B., Davtyan, H., Housley, S. B., Blair, L. J., Gillies, A., Nordhues, B. A., Zhang, B., Liu, J., Gestwicki, J. E., Lee, D. C., et al. (2014) · Journal of Neuroinflammation · doi:10.1186/s12974-014-0152-0 · Cited by 40
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 38
Invited review: Drug development for tauopathies
Grüninger, F. (2014) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12192 · Cited by 40
“…2014 [174] Anti-tau Reduction in tau pathology, improved cognition Yanamandra et al., 2013 [144] Anti-tau oligomers Reduction in tau pathology, improved cognition, functional improvement Castillo-Carranza et al., 2014 [103,104] NAN 2015; 41: 81–96© 2014 British Neuropathological Society in [161]).”
BackgroundRescue from tau-induced neuronal dysfunction produces insoluble tau oligomers
Cowan, C. M., Quraishe, S., Hands, S. L., Sealey, M. A., Mahajan, S., Allan, D. W., & Mudher, A. K. (2015) · Scientific Reports · doi:10.1038/srep17191 · Cited by 41
Azure C Targets and Modulates Toxic Tau Oligomers
Cascio, F. L., & Kayed, R. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00501 · Cited by 41
Self-citationGenetic underpinnings in Alzheimer’s disease – a review
Moustafa, A. A., Hassan, M., Hewedi, D. H., Hewedi, I. H., Garami, J. K., Alashwal, H., Zaki, N., Seo, S., Cutsuridis, V., Angulo, S. L., et al. (2017) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0036 · Cited by 37
“Injecting mutant tau mice with tau oligomer antibodies has shown to improve working memory as well as to maintain the improvement for 2 months (Castillo-Carranza et al., 2014).”
BackgroundMontalbano, M., Majmundar, L., Sengupta, U., Fung, L., & Kayed, R. (2022) · Brain Pathology · doi:10.1111/bpa.13112 · Cited by 35
“We previously showed that TOMA1 and TOMA2 recognized oligomeric tau in P301L tauopathy mouse model and AD, ALS and FTD postmortem brain tissues [20, 21].”
BackgroundSelf-citationShamir, D. B., Rosenqvist, N., Rasool, S., Pedersen, J. T., & Sigurdsson, E. M. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.01.013 · Cited by 34
Current and Emerging Pharmacological Targets for the Treatment of Alzheimer’s Disease
Morsy, A., & Trippier, P. C. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190744 · Cited by 36
“However, no effect was observed in hyperphosphorylated tau or neurofibrillary tangles [131].”
Background“Prion-like” seeding and propagation of oligomeric protein assemblies in neurodegenerative disorders
Zampar, S., Gregorio, S. E. D., Grimmer, G., Watts, J. C., & Ingelsson, M. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1436262 · Cited by 39
Maeda, S., Sato, Y., & Takashima, A. (2018) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2018.04.014 · Cited by 33
Tau as a mediator of neurotoxicity associated to cerebral amyloid angiopathy
You, Y., Perkins, A., Cisternas, P., Muñoz, B., Taylor, X., You, Y., Garringer, H. J., Oblak, A. L., Atwood, B. K., Vidal, R., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0680-z · Cited by 33
“Both MC1 and TOMA antibodies recognized early stages of tau aggregation such as oligomers [11, 37].”
Self-citationAlzheimer’s disease: phenotypic approaches using disease models and the targeting of tau protein
Lauretti, E., & Praticò, D. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1737012 · Cited by 34
Three‐repeat and four‐repeat tau isoforms form different oligomers
Shahpasand‐Kroner, H., Portillo, J., Lantz, C., Seidler, P. M., Sarafian, N., Loo, J. A., & Bitan, G. (2021) · Protein Science · doi:10.1002/pro.4257 · Cited by 32
“To study the oligomerization propensity of different tau isoforms, the purified, recombinant proteins were analyzed first using dot blots probed with antibody Tau Oligomeric specific Complex-1 (TOC1)(36) (Figure 1a), one of several antibodies reported previously to label tau oligomers.(27,29,37) In initial experiment,…”
MethodTargeting Insulin for Alzheimer’s Disease: Mechanisms, Status and Potential Directions
Lee, J. H., Jahrling, J. B., Denner, L. A., & Dineley, K. T. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179923 · Cited by 36
Self-citationTau immunization: a cautionary tale?
Mably, A. J., Kanmert, D., Donald, J. M. M., Liu, W., Caldarone, B. J., Lemere, C. A., O’Nuallain, B., Kosik, K. S., & Walsh, D. M. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.11.022 · Cited by 32
“, 2012) or passive immunization with phospho-specific or conformational-specific anti-tau monoclonal antibodies (mAbs) (Boutajangout et al., 2011; Castillo-Carranza et al., 2014; Chai et al., 2011; d’Abramo et al., 2013; Kontsekova et al., 2014b; Walls et al., 2014; Yanamandra et al., 2013).”
BackgroundAbskharon, R. N. N., Seidler, P. M., Sawaya, M. R., Cascio, D., Yang, T. P., Philipp, S., Williams, C. K., Newell, K. L., Ghetti, B. F., Deture, M. A., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.013638 · Cited by 30
“Passive immunization with anti-tau oligomer antibodies called “tau oligomer mAb” (TOMA) reduced levels of tau oligomers and reversed locomotor and memory deficits in tau P301L mice, suggesting that antibodies that target tau oligomers may be effective therapeutics for AD and various tauopathies (24).”
BackgroundDesai, A. A., Smith, M. D., Zhang, Y., Makowski, E. K., Gerson, J. E., Ionescu, E., Starr, C. G., Zupancic, J. M., Moore, S. J., Sutter, A. B., et al. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100508 · Cited by 31
“, (10, 16, 22, 33, 34)], these approaches typically require extensive secondary screening to identify such rare variants and are not readily extendable to generate conformational antibodies against different sites in the same protein or other proteins in a systematic, efficient, and predictable manner.”
BackgroundSelf-citationDynamic assessment of tau immunotherapies in the brains of live animals by two-photon imaging
Wu, Q., Lin, Y., Gu, J., & Sigurdsson, E. M. (2018) · EBioMedicine · doi:10.1016/j.ebiom.2018.08.041 · Cited by 31
Therapeutic Strategies for Restoring Tau HomeostasisPreprint
Young, Z. T., Mok, S., & Gestwicki, J. E. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024612 · Cited by 31
“…it is likely that oligomers are especially detrimental to cells, because they decrease cell viability more potently than tau fibrils (Flach et al. 2012), and antibodies against oligomers of tau are protective when administered to animal models of tauopathy (Castillo-Carranza et al. 2014, 2015).”
BackgroundDavtyan, H., Chen, W. W., Zagorski, K., Davis, J., Petrushina, I., Kazarian, K., Cribbs, D. H., Agadjanyan, M. G., Blurton-Jones, M., & Ghochikyan, A. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.03.020 · Cited by 30
“Another group tested the Mab specific to oligomeric tau conformational epitope in JNPL3 mouse models of tauopathy and showed a single intravenous (IV) injection of Mab cleared oligomeric tau, rescued the locomotor phenotype, and reversed the memory deficits associated with oligomeric tau pathology [54].”
BackgroundEarly alterations of neurovascular unit in the retina in mouse models of tauopathy
Xia, F., Ha, Y., Shi, S., Li, Y., Li, S., Luisi, J. D., Kayed, R., Motamedi, M., Liu, H., & Zhang, W. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01149-y · Cited by 30
“tau are the main toxic tau species in tauopathies [23, 27], and systemic administration of TOMA reversed neurodegenerative phenotypes in the brain of aged P301L tau transgenic mice [9, 10, 22].”
InfluentialSelf-citationCould a Common Mechanism of Protein Degradation Impairment Underlie Many Neurodegenerative Diseases?
Smith, D. M. (2018) · Journal of Experimental Neuroscience · doi:10.1177/1179069518794675 · Cited by 32
Bhopatkar, A. A., & Kayed, R. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.105122 · Cited by 28
Self-citationGhadge, G. D., Kay, B. K., Drigotas, C., & Roos, R. P. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.08.021 · Cited by 28
Tau Oligomers in Sera of Patients with Alzheimer’s Disease and Aged Controls
Kolarova, M., Sengupta, U., Bartos, A., Ricny, J., & Kayed, R. (2017) · Journal of Alzheimer’s Disease · doi:10.3233/jad-170048 · Cited by 27
Self-citationCellular Biology of Tau Diversity and Pathogenic Conformers
Kang, S., Eskandari‐Sedighi, G., Hromádková, L., Safar, J., & Westaway, D. A. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.590199 · Cited by 29
“Empirically, one way to test for toxicity is by direct injection of purified material and here it is noted that injection of oligomers into the brain of wild-type mice, rather than monomers or fibrils cause cognitive, synaptic, and mitochondrial abnormalities (126, 213).”
BackgroundEllis, M. J., Lekka, C., Holden, K. L., Tulmin, H., Seedat, F., O'Brien, D. P., Dhayal, S., Zeissler, M., Knudsen, J. G., Kessler, B. M., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02729-7 · Cited by 26
“S24-S26), which coincides with the reported MW for low-order Tau oligomers, the very species that T22 and TOMA-1 have been reported to bind to [29, 87], demonstrating that aggregated Tau species, including Tau oligomers, were indeed extracted efficiently from AD human brains.”
BackgroundMethodInfluentialNaturally Occurring Autoantibodies against Tau Protein Are Reduced in Parkinson's Disease Dementia
Kronimus, Y., Albus, A., Balzer‐Geldsetzer, M., Straub, S., Semler, E., Otto, M., Klotsche, J., Dodel, R. C., & Mengel, D. (2016) · PLoS ONE · doi:10.1371/journal.pone.0164953 · Cited by 26
The Structure Biology of Tau and Clue for Aggregation Inhibitor Design
Wang, D., Huang, X., Yan, L., Zhou, L., Chang, Y., Wu, J., Su, Z., & Huang, Y. (2021) · The Protein Journal · doi:10.1007/s10930-021-10017-6 · Cited by 27
Bajracharya, R., Cruz, E., Götz, J., & Nisbet, R. M. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.07.026 · Cited by 27
Therapeutic and diagnostic challenges for frontotemporal dementia
Dâ€TMAlton, S., & Lewis, J. M. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00204 · Cited by 26
“Although tau has long been recognized as the principle component of neurofibrillary tangles (NFTs) in FTD (Joachim et al., 1987) and mutations in the microtubule associated protein tau (MAPT) are responsible for a subset of FTD cases (Hutton et al., 1998; Spillantini et al., 1998; D’Souza et al., 1999), investment in…”
BackgroundInfluentialHa, Y., Liu, W., Liu, H., Zhu, S., Xia, F., Gerson, J. E., Azhar, N. A., Tilton, R. G., Motamedi, M., Kayed, R., et al. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.18-24427 · Cited by 25
“Studies have shown that intravenous delivery of TOMA neutralized extracellular tau oligomers and promoted the egress of intracellular oligomeric tau, resulting in a net decrease of tau oligomers in the CNS and eventual serum clearance, and reversed the neurodegenerative phenotypes in aged P301L tau transgenic mice.(18…”
Self-citationPassive immunization against phosphorylated tau improves features of Huntington's disease pathology
Alpaugh, M., Masnata, M., de Rus Jacquet, A., Lepinay, E., Denis, H. L., Saint-Pierre, M., Davies, P., Planel, E., & Cicchetti, F. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.020 · Cited by 25
Oligomeric tau-targeted immunotherapy in Tg4510 mice
Schroeder, S. K., Joly‐Amado, A., Soliman, A. S., Sengupta, U., Kayed, R., Gordon, M. N., & Morgan, D. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0274-6 · Cited by 24
“These results were unexpected based on the behavioral improvements in Y-maze performance in the initial publication of this treatment [17].”
InfluentialSelf-citationNg, P. Y., Chang, I. S., Koh, R. Y., & Chye, S. M. (2020) · Metabolic Brain Disease · doi:10.1007/s11011-020-00591-6 · Cited by 25
“Studies also demonstrated JNPL3 mice administered with Tau oligomer-specific monoclonal antibody (TOMA) have their Tau oligomers being decreased and memory and locomotor deficits being reversed (Castillo-Carranza et al., 2014a; Rosenqvist et al. 2018).”
BackgroundResultHeterogeneous Tau Oligomers as Molecular Targets for Alzheimer’s Disease and Related Tauopathies
Lo, C. H. (2022) · Biophysica · doi:10.3390/biophysica2040039 · Cited by 24
“The administration of TOMA to mice expression human tau has shown to be effective in reducing tau oligomers and rescuing memory deficits [121,126].”
Albayram, Ö., MacIver, B., Mathai, J., Verstegen, A. M. J., Baxley, S., Qiu, C., Bell, C. A., Caldarone, B. J., Zhou, X. Z., Lu, K. P., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-45234-8 · Cited by 26
Chandupatla, R., Flatley, A., Feederle, R., Mandelkow, E., & Kaniyappan, S. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12097 · Cited by 23
Maeda, S., & Takashima, A. (2019) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-32-9358-8_27 · Cited by 22
Intraneuronal Tau Misfolding Induced by Extracellular Amyloid-β Oligomers
Rudenko, L. K., Wallrabe, H. K., Periasamy, A., Siller, K. H., Švindrych, Z., Seward, M. E., Best, M. N., & Bloom, G. S. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190226 · Cited by 24
“Several methods are well established for detecting aggregated tau, including binding of Congo red [45], and a variety of antibodies spe-cific for oligomeric or fibrillar tau [46, 47], and PET imaging that can detect neurofibrillary tangles in live patients [48].”
Panza, F., Dibello, V., Sardone, R., Castellana, F., Zupo, R., Lampignano, L., Bortone, I., Stallone, R., Cirillo, N., Damiani, C., et al. (2023) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2023.2233892 · Cited by 22
An evaluation of Drosophila as a model system for studying tauopathies such as Alzheimer’s disease
Sivanantharajah, L., Mudher, A. K., & Shepherd, D. (2019) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2019.01.001 · Cited by 23
“targeting tau oligomers reverses tauopathy phenotypes in a rodent model of tauopathy (Castillo-Carranza et al. 2014).”
BackgroundNasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice
Takeuchi, H., Imamura, K., Ji, B., Tsukita, K., Enami, T., Takao, K., Miyakawa, T., Hasegawa, M., Sahara, N., Iwata, N., et al. (2020) · npj Vaccines · doi:10.1038/s41541-020-0172-y · Cited by 22
Targeting Tau to Treat Clinical Features of Huntington's Disease
Masnata, M., Salem, S., Jacquet, A. D. R., Anwer, M., & Cicchetti, F. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.580732 · Cited by 25
“Several peptides have been designed using tau pathological forms such as p-tau (181, 183), oligomers (180, 184) and truncated tau (185).”
MethodBodani, R. U., Sengupta, U., Castillo‐Carranza, D. L., Guerrero‐Munoz, M. J., Gerson, J. E., Rudra, J. S., & Kayed, R. (2015) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5b00231 · Cited by 21
Self-citationSevere oligomeric tau toxicity can be reversed without long-term sequelae
Martinisi, A., Flach, M., Sprenger, F., Frank, S., Tolnay, M., & Winkler, D. T. (2020) · Brain · doi:10.1093/brain/awaa445 · Cited by 22
“Strikingly, interventions with compounds targeting tau oligomers have already shown beneficial effects, including the reversal of brain dysfunction (Castillo-Carranza et al., 2014; Soeda et al., 2015; Gerson et al., 2018; Lo Cascio et al., 2019; Lo et al., 2019).”
BackgroundChopra, G., Shabir, S., Yousuf, S., Kauts, S., Bhat, S. A., Mir, A. H., & Singh, M. P. (2022) · Molecular Neurobiology · doi:10.1007/s12035-022-03042-8 · Cited by 24
Arastoo, M., Lofthouse, R. A., Penny, L. K., Harrington, C. R., Porter, A., Wischik, C. M., & Palliyil, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228673 · Cited by 21
“However, there are few tau oligomer-specific antibodies currently available [83,84].”
BackgroundLasagna‐Reeves, C. A., Rousseaux, M. W. C., Guerrero‐Munoz, M. J., Vilanova-Velez, L., Park, J., See, L., Jafar‐Nejad, P., Richman, R., Orr, H. T., Kayed, R., et al. (2015) · eLife · doi:10.7554/elife.10891 · Cited by 20
“Passive immunotherapy has been proposed as a feasible strategy to inhibit pathogenesis in mouse models for AD and PD (Banks et al., 2007; Chai et al., 2011; Masliah et al., 2011; Yanamandra et al., 2013; Castillo-Carranza et al., 2014; Games et al., 2014).”
BackgroundSelf-citationPreparation and Characterization of Tau Oligomer Strains
Sengupta, U., Murillo, M. C., & Kayed, R. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7816-8_9 · Cited by 20
Self-citationMessenger RNA-encoded antibody approach for targeting extracellular and intracellular tau
Wongsodirdjo, P., Caruso, A. C., Yong, A., Lester, M. A., Vella, L. J., Hung, Y. H., & Nisbet, R. M. (2024) · Brain Communications · doi:10.1093/braincomms/fcae100 · Cited by 20
Human Truncated Tau Induces Mature Neurofibrillary Pathology in a Mouse Model of Human Tauopathy
Zimova, I., Brezováková, V., Hromádka, T., Weisová, P., Cubinkova, V., Valachova, B., Filipčík, P., Jadhav, S., Smolek, T., Novák, M., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160347 · Cited by 19
“…transgenic mice with oligomer-specific monoclonal antibody (TOMA) designed to intervene with tau oligomers that occur in the brain before NFTs formation was sufficient to alter behavioral deficits in mice and led to striking reduction of tau oligomers but not phosphorylated NFTs or monomeric tau [17].”
Targeting Prion-like Cis Phosphorylated Tau Pathology in Neurodegenerative Diseases
Albayram, Ö., Angeli, P. A., Bernstein, E. R., Baxley, S., Gao, Z. J., Lu, K. P., & Zhou, X. Z. (2018) · Journal of Alzheimer’s Disease & Parkinsonism · doi:10.4172/2161-0460.1000443 · Cited by 19
“Recent roadblocks to the progression of Aβ-targeted therapies, along with the new concept of prion-like propagation of intracellular abnormal proteins, have brought tau into the spotlight as a potential therapeutic target [12-20].”
Bittar, A., Al-Lahham, R., Bhatt, N., Moore, K., Montalbano, M., Jerez, C., Fung, L., McAllen, S., Ellsworth, A., & Kayed, R. (2022) · Journal of Alzheimer's Disease · doi:10.3233/jad-220518 · Cited by 18
Self-citationBasurto‐Islas, G., Diaz, M. C., Zavala-Ocampo, L. M., Martínez‐Herrera, M., & López-Camacho, P. Y. (2025) · Archiv der Pharmazie · doi:10.1002/ardp.202400721 · Cited by 20
Hromádková, L., Kolarova, M., Jankovičová, B., Bartoš, A., Říčný, J., Bı́lková, Z., & Řı́pová, D. (2015) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2015.10.017 · Cited by 18
Pathogenic Tau Protein Species: Promising Therapeutic Targets for Ocular Neurodegenerative Diseases
Mishan, M. A., Kanavi, M. R., Shahpasand, K., & Ahmadieh, H. (2019) · Journal of Ophthalmic and Vision Research · doi:10.18502/jovr.v14i4.5459 · Cited by 18
Clearing the way for tau immunotherapy in Alzheimer's disease
Herrmann, A. G., & Spires‐Jones, T. L. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12845 · Cited by 18
Wu, Q., Bai, Y., Li, W., Congdon, E. E., Liu, W., Lin, Y., Ji, C., Gan, W., & Sigurdsson, E. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105165 · Cited by 15
Current Understanding of Protein Aggregation in Neurodegenerative Diseases
Hu, C., Lin, M., Wang, C., & Zhang, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262110568 · Cited by 21
Implications of Tau Dysregulation in Huntington’s Disease and Potential for New Therapeutics
Mees, I., Nisbet, R. M., Hannan, A. J., & Renoir, T. (2023) · Journal of Huntington s Disease · doi:10.3233/jhd-230569 · Cited by 16
Davidson, R., Krider, R. I., Borsellino, P., Noorda, K., Alhwayek, G., & Vida, T. A. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45110553 · Cited by 17
“Mice injected with tau oligomers exhibited more severe cognitive and neuronal abnormalities compared to those injected with other tau forms like NFTs [65,66].”
BackgroundFrontotemporal Lobar Degeneration: Mechanisms and Therapeutic Strategies
Li, Y., Tan, M., Yu, J., & Tan, L. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9507-5 · Cited by 17
“In addition, immunotherapy reversed P301L motor and memory phenotypes and specially cleared tau oligomers, without altering NFTs, and this immunotherapy would have the additional benefit of halting the cell-to-cell spread of tau pathology [61].”
BackgroundGazzina, S., Manes, M. A., Padovani, A., & Borroni, B. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.05.056 · Cited by 21
Jiang, L., Roberts, R., Wong, M., Zhang, L., Webber, C. J., Libera, J., Wang, Z., Kilci, A., Jenkins, M., Ortiz, A. R., et al. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1372297 · Cited by 15
Intracellular tau fragment droplets serve as seeds for tau fibrils
Soeda, Y., Yoshimura, H., Bannai, H., Koike, R., Shiiba, I., & Takashima, A. (2024) · Structure · doi:10.1016/j.str.2024.06.018 · Cited by 15
Marvian, A. T., Strauß, T., Tang, Q., Tuck, B. J., Keeling, S., Rüdiger, D., Dizaji, N. M., Mohammad‐Beigi, H., Nuscher, B., Chakraborty, P., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00786-w · Cited by 16
“…pathological conformation [29]; TOMA-1 (1:500; MABN819, Merck Millipore, Billerica, MA) being an anti-Tau oligomer-specific conformational antibody [30]; MC1 (1:500; a gift from Dr. Peter Davis) indicating a pathological conformation by binding two discontinues AD-specific epitopes at N-terminal…”
Zaghmi, A., Drouin‐Ouellet, J., Brambilla, D., & Gauthier, M. A. (2020) · Biomaterials · doi:10.1016/j.biomaterials.2020.120461 · Cited by 17
Nieznańska, H., Boyko, S., Dec, R., Rędowicz, M. J., Dzwolak, W., & Nieznański, K. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166209 · Cited by 16
Tai, H., Ma, H.-T., Huang, S.-C., Wu, M., Wu, C., Lai, Y., Li, Z., Margolin, R. A., Intorcia, A. J., Serrano, G. E., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.24.497452 · Cited by 15
Tang, J., Zou, Y. F., Gong, Y., Xu, Z., Wan, J., Wei, G., & Zhang, Q. (2023) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.2c00688 · Cited by 14
Krestová, M., Hromádková, L., Bı́lková, Z., Bartoš, A., & Říčný, J. (2017) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2017.09.011 · Cited by 13
Zhan, X., Wen, G., Wu, X., & Li, J. (2025) · Translational Neurodegeneration · doi:10.1186/s40035-025-00490-9 · Cited by 14
Pin1-Catalyzed Conformation Changes Regulate Protein Ubiquitination and Degradation
Jeong, J., Usman, M., Li, Y., Zhou, X. Z., & Lu, K. P. (2024) · Cells · doi:10.3390/cells13090731 · Cited by 14
FTLD Treatment: Current Practice and Future Possibilities
Ljubenkov, P. A., & Boxer, A. L. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-51140-1_18 · Cited by 16
Detection of misfolded protein aggregates from a clinical perspective
Strømland, Ø., Jakubec, M., Furse, S., & Halskau, Ø. (2016) · Journal of Clinical and Translational Research · doi:10.18053/jctres.02.201601.003 · Cited by 12
“For these reasons, false positive results Table 3a. Oligomeric protein states detected by antibodies Aggregating protein Antibody Specificity and epitope Cross-reactions Detection Methods and References Aβ-peptide 4G8 Recognizes residue 18-23 in Aβ sequence, in its fibrils and fibrillary oligomers form α-Syn, IAPP, Ta…”
BackgroundInfluentialBöken, D., Wu, Y., Zhang, Z.-W., & Klenerman, D. (2024) · ChemBioChem · doi:10.1002/cbic.202400877 · Cited by 11
Metadata
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
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