Antisense Reduction of Tau in Adult Mice Protects against Seizures
Open accessAbstract
Tau, a microtubule-associated protein, is implicated in the pathogenesis of Alzheimer's Disease (AD) in regard to both neurofibrillary tangle formation and neuronal network hyperexcitability. The genetic ablation of tau substantially reduces hyperexcitability in AD mouse lines, induced seizure models, and genetic in vivo models of epilepsy. These data demonstrate that tau is an important regulator of network excitability. However, developmental compensation in the genetic tau knock-out line may account for the protective effect against seizures. To test the efficacy of a tau reducing therapy for disorders with a detrimental hyperexcitability profile in adult animals, we identified antisense oligonucleotides that selectively decrease endogenous tau expression throughout the entire mouse CNS--brain and spinal cord tissue, interstitial fluid, and CSF--while having no effect on baseline motor or cognitive behavior. In two chemically induced seizure models, mice with reduced tau protein had less severe seizures than control mice. Total tau protein levels and seizure severity were highly correlated, such that those mice with the most severe seizures also had the highest levels of tau. Our results demonstrate that endogenous tau is integral for regulating neuronal hyperexcitability in adult animals and suggest that an antisense oligonucleotide reduction of tau could benefit those with epilepsy and perhaps other disorders associated with tau-mediated neuronal hyperexcitability.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
ASO-mediated tau reduction has shown promising results in the treatment of Alzheimer's disease after local injection of Tau-ASO using an intracerebroventricular pump.
“because ASO-mediated tau reduction has shown promising results in the treatment of Alzheimer’s disease after the local injection of the Tau-ASO using an intracerebroventricular (ICV) pump (31, 32).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [31]
The Results section reports that Tau-ASO delivered by intracerebroventricular pumps reduced tau in adult mice. The Discussion describes treatment of Alzheimer’s disease as a possible future application, not a demonstrated result: this paper studied seizure protection, not treatment efficacy in Alzheimer’s disease. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn a previous study, ~80% reduction of tau mRNA and ~70% reduction of tau protein were achieved by continuously dosing 28 days with 25-μg Tau-ASO per day through local injection by ICV pump.
“Notably, in the previous study, ~80% reduction of tau mRNA and ~70% reduction of tau protein were achieved by continuously dosing 28 days, and the dose was 25-μg Tau-ASO per day through local injection by ICV pump (31).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [31]
The Methods describe 28-day ICV osmotic pumps, and the Results section on endogenous tau expression reports that 25 μg/day Tau ASO-3 reduced tau mRNA by more than 75%, with a reduction exceeding 80% still present four weeks after infusion stopped. The Results also report reduced tau protein after this treatment, but our copy does not give the claimed approximately 70% protein reduction. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAcross various animal models that exhibit epilepsy, reducing tau levels reduces network hyperexcitability, seizure severity, and latency to seizure stages.
“Across various animal models that exhibit epilepsy, reducing tau levels reduces network hyperexcitability, seizure severity, and latency to seizure stages (Roberson et al., 2007; Ittner et al., 2010; DeVos et al., 2013; Holth et al., 2013; Wang and Mandelkow, 2016; Ali et al., 2019).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as DeVos et al., 2013
The Abstract reports that tau reduction made seizures less severe in two chemically induced mouse models, and the Introduction discusses reduced hyperexcitability across other mouse models. But the Results section on intrinsic tau variability reports that mice with lower tau took longer—not less time—to reach a stage 8 seizure. The claim reverses the direction of seizure latency. (LLM, conf=0.90)
Experimental — accuracy not yet measuredEndogenous levels of tau positively correlate with chemically induced seizure susceptibility in wild-type mice.
“Endogenous levels of tau also positively correlate with chemically induced seizure susceptibility in wild-type mice (DeVos et al., 2013), suggesting a role of endogenous tau in mediating epileptic activity.”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as DeVos et al., 2013
Endogenous tau likely contributes to network hyperexcitability across primary and secondary epilepsies.
“Given tau’s role in modulating neuronal activity under normal physiological conditions (DeVos et al., 2013; Chang et al., 2021), endogenous tau likely contributes to network hyperexcitability across primary and secondary epilepsies.”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as DeVos et al., 2013
Endogenous murine tau reduction in adult mice results in no behavioral or neuroanatomical abnormalities.
“Our group has previously shown that endogenous murine tau reduction in adult mice results in no behavioral or neuroanatomical abnormalities, supporting the viability of a tau lowering therapy (15).”
From Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy (2017) · cites this paper as [15]
When endogenous murine tau is reduced in adult mice, no deviations from baseline are seen in any sensory, motor, or cognitive behavior task.
“Importantly, when endogenous murine tau is reduced in adult mice, no deviations from baseline are seen in any sensory, motor, or cognitive behavior task (15), adding support to the safety of reducing tau in the adult mammalian brain.”
From Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy (2017) · cites this paper as [15]
Lowering tau in adult mice with a tau ASO was protective against seizures.
“Our previous work emphasized this point by demonstrating that lowering tau in adult mice with a tau ASO was also protective against seizures (15).”
From Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy (2017) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Modification of seizure activity by electrical stimulation: II. Motor seizure
Racine, R. J. (1972) · Electroencephalography and Clinical Neurophysiology · doi:10.1016/0013-4694(72)90177-0 · Cited by 7,141 · see citing works
A protein factor essential for microtubule assembly
Weingarten, M. D., Lockwood, A. H., Hwo, S. Y., & Kirschner, M. W. (1975) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.72.5.1858 · Cited by 3,089 · see citing works
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · 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
Gene regulation and DNA damage in the ageing human brain
Lu, T., Pan, Y., Kao, S.-Y., Li, C., Kohane, I., Chan, J., & Yankner, B. A. (2004) · Nature · doi:10.1038/nature02661 · Cited by 1,874 · see citing works
Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models
Ittner, L. M., Ke, Y. D., Delerue, F., Bi, M., Gladbach, A., van Eersel, J., Wölfing, H., Chieng, B. C., Christie, M. J., Napier, I. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.036 · Cited by 1,821 · see citing works
Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection
Lanford, R. E., Hildebrandt-Eriksen, E. S., Petri, A., Persson, R., Lindow, M., Munk, M. E., Kauppinen, S., & Ørum, H. (2009) · Science · doi:10.1126/science.1178178 · Cited by 1,654 · see citing works
Bennett, C. F., & Swayze, E. E. (2010) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105654 · Cited by 1,381 · see citing works
Self-citationA population-based study of seizures after traumatic brain injuries
Annegers, J. F., Hauser, W. A., Coan, S. P., & Rocca, W. A. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801013380104 · Cited by 1,090 · see citing works
Löscher, W. (2011) · Seizure · doi:10.1016/j.seizure.2011.01.003 · Cited by 933 · see citing works
Patterns of treatment response in newly diagnosed epilepsy
Brodie, M. J., Barry, S., Bamagous, G. A., Norrie, J. D., & Kwan, P. (2012) · Neurology · doi:10.1212/wnl.0b013e3182563b19 · Cited by 931 · see citing works
Reduction of Hippocampal Hyperactivity Improves Cognition in Amnestic Mild Cognitive Impairment
Bakker, A., Krauss, G. L., Albert, M., Speck, C. L., Jones, L. R., Stark, C. E. L., Yassa, M. A., Bassett, S. S., Shelton, A. L., & Gallagher, M. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.023 · Cited by 905 · see citing works
Neuronal activity regulates the regional vulnerability to amyloid-β deposition
Bero, A. W., Yan, P., Roh, J. H., Cirrito, J. R., Stewart, F. R., Raichle, M. E., Lee, J.-M., & Holtzman, D. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2801 · Cited by 880 · see citing works
Self-citationAltered microtubule organization in small-calibre axons of mice lacking tau protein
Harada, A., Oguchi, K., Okabe, S., Kuno, J., Terada, S., Ohshima, T., Sato-Yoshitake, R., Takei, Y., Noda, T., & Hirokawa, N. (1994) · Nature · doi:10.1038/369488a0 · Cited by 806 · see citing works
Kordasiewicz, H. B., Stanek, L. M., Wancewicz, E. V., Mazur, C., McAlonis, M. M., Pytel, K. A., Artates, J. W., Weiss, A., Cheng, S. H., Shihabuddin, L. S., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.05.009 · Cited by 770 · see citing works
Self-citationSeizures and Epileptiform Activity in the Early Stages of Alzheimer Disease
Vossel, K. A., Beagle, A. J., Rabinovici, G. D., Shu, H., Lee, S. E., Naasan, G., Hegde, M., Cornes, S. B., Henry, M. L., Nelson, A., et al. (2013) · JAMA Neurology · doi:10.1001/jamaneurol.2013.136 · Cited by 730 · see citing works
Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse modelPreprint
Hua, Y., Sahashi, K., Hung, G., Rigo, F., Passini, M. A., Bennett, C. F., & Krainer, A. R. (2010) · Genes & Development · doi:10.1101/gad.1941310 · Cited by 665 · see citing works
Self-citationRoberson, E. D., Halabisky, B., Yoo, J. W., Yao, J., Chin, J., Yan, F., Wu, T., Hamto, P., Devidze, N., Yu, G.-Q., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4152-10.2011 · Cited by 654 · see citing works
Physiological release of endogenous tau is stimulated by neuronal activity
Pooler, A. M., Phillips, E. C., Lau, D. H. W., Noble, W., & Hanger, D. P. (2013) · The EMBO Reports · doi:10.1038/embor.2013.15 · Cited by 642 · see citing works
Sanchez, P. E., Zhu, L., Verret, L., Vossel, K. A., Orr, A. G., Cirrito, J. R., Devidze, N., Ho, K., Yu, G.-Q., Palop, J. J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121081109 · Cited by 638 · see citing works
Self-citationEndocytosis Is Required for Synaptic Activity-Dependent Release of Amyloid-β In Vivo
Cirrito, J. R., Kang, J.-E., Lee, J., Stewart, F. R., Verges, D. K., Silverio, L. M., Bu, G., Mennerick, S., & Holtzman, D. M. (2008) · Neuron · doi:10.1016/j.neuron.2008.02.003 · Cited by 635 · see citing works
Self-citationMiller, T. M., Pestronk, A., David, W., Rothstein, J., Simpson, E., Appel, S. H., Andres, P. L., Mahoney, K., Allred, P., Alexander, K., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70061-9 · Cited by 617 · see citing works
Self-citationTau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export
Lei, P., Ayton, S., Finkelstein, D. I., Spoerri, L., Ciccotosto, G. D., Wright, D. K., Wong, B. X. W., Adlard, P. A., Cherny, R. A., Lam, L. Q., et al. (2012) · Nature Medicine · doi:10.1038/nm.2613 · Cited by 594 · see citing works
Incidence and Predictors of Seizures in Patients with Alzheimer's Disease
Amatniek, J. C., Hauser, W. A., del Castillo–Castañeda, C., Jacobs, D. M., Marder, K. S., Bell, K. L., Albert, M., Brandt, J., & Stern, Y. (2006) · Epilepsia · doi:10.1111/j.1528-1167.2006.00554.x · Cited by 592 · see citing works
Passini, M. A., Bu, J., Richards, A. M., Kinnecom, C., Sardi, S. P., Stanek, L. M., Hua, Y., Rigo, F., Matson, J. E., Hung, G., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3001777 · Cited by 547 · see citing works
Self-citationNeurotrophins are required for nerve growth during development
Tucker, K. L., Meyer, M., & Barde, Y. (2001) · Nature Neuroscience · doi:10.1038/82868 · Cited by 526 · see citing works
Antisense oligonucleotide therapy for neurodegenerative disease
Smith, R. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25424 · Cited by 506 · see citing works
Suberbielle, E., Sanchez, P. E., Kravitz, A. V., Wang, X., Ho, K., Eilertson, K., Devidze, N., Kreitzer, A. C., & Mucke, L. (2013) · Nature Neuroscience · doi:10.1038/nn.3356 · Cited by 487 · see citing works
Tau Reduction Prevents Aβ-Induced Defects in Axonal Transport
Vossel, K. A., Zhang, K., Brodbeck, J., Daub, A. C., Sharma, P., Finkbeiner, S., Cui, B., & Mucke, L. (2010) · Science · doi:10.1126/science.1194653 · Cited by 486 · see citing works
Billingsley, M., & Kincaid, R. (1997) · Biochemical Journal · doi:10.1042/bj3230577 · Cited by 469 · see citing works
Seizures and Epilepsy After Ischemic Stroke
Camilo, O., & Goldstein, L. B. (2004) · Stroke · doi:10.1161/01.str.0000130989.17100.96 · Cited by 429 · see citing works
Efficacy of systemic morpholino exon‐skipping in duchenne dystrophy dogs
Yokota, T., Lu, Q., Partridge, T. A., Kobayashi, M., Nakamura, A., Takeda, S., & Hoffman, E. P. (2009) · Annals of Neurology · doi:10.1002/ana.21627 · Cited by 398 · see citing works
GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease
Cruchaga, C., Kauwe, J. S. K., Harari, O., Jin, S. C., Cai, Y., Karch, C. M., Benitez, B. A., Jeng, A. T., Skorupa, T., Carrell, D., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.026 · Cited by 383 · see citing works
Self-citationBuée, L., & Delacourte, A. (1999) · Brain Pathology · doi:10.1111/j.1750-3639.1999.tb00550.x · Cited by 361 · see citing works
Yamada, K., Cirrito, J. R., Stewart, F. R., Jiang, H., Finn, M. B., Holmes, B. B., Binder, L. I., Mandelkow, E.-M., Diamond, M. I., Lee, V. M.-Y., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2569-11.2011 · Cited by 351 · see citing works
Self-citationDiverse mechanisms of antiepileptic drugs in the development pipeline
Rogawski, M. A. (2006) · Epilepsy Research · doi:10.1016/j.eplepsyres.2006.02.004 · Cited by 340 · see citing works
Fagan, A. M., Head, D., Shah, A. R., Marcus, D., Mintun, M., Morris, J. C., & Holtzman, D. M. (2009) · Annals of Neurology · doi:10.1002/ana.21559 · Cited by 327 · see citing works
Self-citationAndrews-Zwilling, Y., Bien-Ly, N., Xu, Q., Li, G., Bernardo, A., Yoon, S. Y., Zwilling, D., Yan, T. X., Chen, L., & Huang, Y. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4040-10.2010 · Cited by 326 · see citing works
Nonconvulsive seizures after traumatic brain injury are associated with hippocampal atrophy
Vespa, P. M., McArthur, D. L., Xu, Y.-Q., Eliseo, M., Etchepare, M., Dinov, I. D., Alger, J. R., Glenn, T. P., & Hovda, D. A. (2010) · Neurology · doi:10.1212/wnl.0b013e3181f07334 · Cited by 313 · see citing works
Wozniak, D. F., Hartman, R. E., Boyle, M. A., Vogt, S. K., Brooks, A., Tenkova, T. I., YOUNG, C., Olney, J. W., & Muglia, L. J. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.08.006 · Cited by 302 · see citing works
Self-citationLovestone, S., & Reynolds, C. H. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00577-5 · Cited by 278 · see citing works
Macdonald, R. L., & Barker, J. L. (1977) · Nature · doi:10.1038/267720a0 · Cited by 259 · see citing works
Patients with Refractory Seizures
Devinsky, O. (1999) · New England Journal of Medicine · doi:10.1056/nejm199905203402008 · Cited by 257 · see citing works
Myers, A., Pittman, A. M., Zhao, A. S., Rohrer, K., Kaleem, M. A., Marlowe, L., Lees, A. J., Leung, D. G., McKeith, I. G., Perry, R. H., et al. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.10.018 · Cited by 254 · see citing works
Trabzuni, D., Wray, S., Vandrovcova, J., Ramasamy, A., Walker, R., Smith, C., Luk, C., Gibbs, J. R., Dillman, A., Hernandez, D. G., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds238 · Cited by 252 · see citing works
Kempf, M., Clement, A. M., Faissner, A., Lee, G. S., & Brandt, R. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-18-05583.1996 · Cited by 248 · see citing works
A single administration of morpholino antisense oligomer rescues spinal muscular atrophy in mouse
Porensky, P. N., Mitrpant, C., McGovern, V. L., Bevan, A. K., Foust, K. D., Kaspar, B. K., Wilton, S. D., & Burghes, A. H. M. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr600 · Cited by 248 · see citing works
Holth, J. K., Bomben, V. C., Reed, J. G., Inoue, T., Younkin, L., Younkin, S. G., Pautler, R. G., Botas, J., & Noebels, J. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3191-12.2013 · Cited by 238 · see citing works
Glasscock, E., Yoo, J. W., Chen, T. T., Klassen, T., & Noebels, J. L. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5591-09.2010 · Cited by 232 · see citing works
McKay, R. A., Miraglia, L. J., Cummins, L. L., Owens, S. R., Sasmor, H. M., & Dean, N. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.3.1715 · Cited by 220 · see citing works
Seizures in Elderly Patients with Dementia
Mendez, M. F., & Lim, G. T. H. (2003) · Drugs & Aging · doi:10.2165/00002512-200320110-00001 · Cited by 219 · see citing works
Brion, J., Passareiro, H., Nunez, J., & Durand, J. F. (1985) · Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) · Cited by 197 · see citing works
Kumar, V. B., Farr, S. A., Flood, J. F., Kamlesh, V., Franko, M. W., Banks, W. A., & Morley, J. E. (2000) · Peptides · doi:10.1016/s0196-9781(00)00339-9 · Cited by 193 · see citing works
Excitotoxic Neurodegeneration in Alzheimer Disease
Olney, J. W. (1997) · Archives of Neurology · doi:10.1001/archneur.1997.00550220042012 · Cited by 190 · see citing works
CSF biomarkers of Alzheimer disease in HIV-associated neurologic disease
Clifford, D. B., Fagan, A. M., Holtzman, D. M., Morris, J. C., Teshome, M., Shah, A. R., & Kauwe, J. S. K. (2009) · Neurology · doi:10.1212/wnl.0b013e3181c5b445 · Cited by 186 · see citing works
Self-citationMandhane, S. N., Aavula, K., & Rajamannar, T. (2007) · Seizure · doi:10.1016/j.seizure.2007.05.005 · Cited by 179 · see citing works
Direct Intraventricular Delivery of Drugs to the Rodent Central Nervous System
DeVos, S. L., & Miller, T. M. (2013) · Journal of Visualized Experiments · doi:10.3791/50326 · Cited by 174 · see citing works
Self-citationAmyloid-β signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer's disease
Seward, M. E., Swanson, E., Norambuena, A., Reimann, A., Cochran, J. N., Li, R., Roberson, E. D., & Bloom, G. S. (2013) · Journal of Cell Science · doi:10.1242/jcs.1125880 · Cited by 170 · see citing works
Antisense oligonucleotides: treating neurodegeneration at the level of RNA
DeVos, S. L., & Miller, T. M. (2013) · Neurotherapeutics · doi:10.1007/s13311-013-0194-5 · Cited by 164 · see citing works
Self-citationLeroy, K., Ando, K., Laporte, V., Dedecker, R., Suain, V., Authelet, M., Héraud, C., Pierrot, N., Yilmaz, Z., Octave, J.-N., et al. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.08.012 · Cited by 161 · see citing works
Löscher, W., & Nolting, B. (1991) · Epilepsy Research · doi:10.1016/0920-1211(91)90041-d · Cited by 157 · see citing works
Altered Stress-Induced Anxiety in Adenylyl Cyclase Type VIII-Deficient Mice
Schaefer, M. L., Wong, S. T., Wozniak, D. F., Muglia, L. M., Liauw, J. A., Zhuo, M., Nardi, A., Hartman, R. E., Vogt, S. K., Luedke, C. E., et al. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-13-04809.2000 · Cited by 152 · see citing works
Self-citationLoss of tau elicits axonal degeneration in a mouse model of Alzheimer's disease
Dawson, H. N., Cantillana, V., Jansen, M., Wang, H., Vitek, M. P., Wilcock, D. M., Lynch, J., & Laskowitz, D. T. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.04.037 · Cited by 137 · see citing works
Yu, R. Z., Lemonidis, K. M., Graham, M. J., Matson, J. E., Crooke, R. M., Tribble, D. L., Wedel, M. K., Levin, A. A., & Geary, R. S. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.11.005 · Cited by 125 · see citing works
Age-appropriate cognition and subtle dopamine-independent motor deficits in aged Tau knockout mice
Morris, M., Hamto, P., Adame, A., Devidze, N., Masliah, E., & Mucke, L. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.12.003 · Cited by 117 · see citing works
Vogt, D. L., Thomas, D., Galván, V., Bredesen, D. E., Lamb, B. T., & Pimplikar, S. W. (2009) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.09.002 · Cited by 113 · see citing works
Wozniak, D. F., Xiao, M.-L., Xu, L., Yamada, K. A., & Ornitz, D. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.11.014 · Cited by 104 · see citing works
Self-citationPicrotoxin-like channel blockers of GABA A receptors
Olsen, R. W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601121103 · Cited by 102 · see citing works
Cerebellar Synaptic Defects and Abnormal Motor Behavior in Mice Lacking α- and β-Dystrobrevin
Grady, R. M., Wozniak, D. F., Ohlemiller, K. K., & Sanes, J. R. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4823-05.2006 · Cited by 100 · see citing works
Self-citationKauwe, J. S. K., Cruchaga, C., Mayo, K., Fenoglio, C., Bertelsen, S. E., Nowotny, P., Galimberti, D., Scarpini, E. A., Morris, J. C., Fagan, A. M., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801227105 · Cited by 89 · see citing works
Self-citationTau Transgenic Mice as Models for Cerebrospinal Fluid Tau Biomarkers
Barten, D. M., Cadelina, G. W., Hoque, N., DeCarr, L. B., Guss, V. L., Yang, L., Sankaranarayanan, S., Wes, P. D., Flynn, M. E., Meredith, J. E., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110161 · Cited by 87 · see citing works
Velez‐Pardo, C., Arellano, J. I., Cardona‐Gómez, G. P., Jiménez-Del-Río, M., Lopera, F. J., & DeFelipe, J. (2004) · Epilepsia · doi:10.1111/j.0013-9580.2004.55403.x · Cited by 70 · see citing works
Direct Intraventricular Delivery of Drugs to the Rodent Central Nervous System
DeVos, S. L., & Miller, T. M. (2013) · Journal of Visualized Experiments · doi:10.3791/50326-v · Cited by 56 · see citing works
Self-citationCerebrospinal fluid tau as a marker of neuronal damage after epileptic seizure
Palmio, J., Suhonen, J., Keränen, T., Hulkkonen, J., Peltola, J., & Pirttilä, T. (2009) · Seizure · doi:10.1016/j.seizure.2009.04.006 · Cited by 55 · see citing works
Takao, M., Ghetti, B. F., Murrell, J. R., Unverzagt, F. W., Giaccone, G., Tagliavini, F., Bugiani, O., Piccardo, P., Hulette, C. M., Crain, B. J., et al. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.12.1137 · Cited by 50 · see citing works
Iqbal, K., Wı́sniewski, H. M., Grundke, I., Korthals, J. K., & Terry, R. D. (1975) · Journal of Histochemistry & Cytochemistry · doi:10.1177/23.7.1141687 · Cited by 49 · see citing works
Emergence of a seizure phenotype in aged apolipoprotein epsilon 4 targeted replacement mice
Hunter, J. M., Cirrito, J. R., Restivo, J. L., Kinley, R. D., Sullivan, P. M., Holtzman, D. M., Koger, D., Delong, C., Lin, S., Zhao, L., et al. (2012) · Brain Research · doi:10.1016/j.brainres.2012.05.048 · Cited by 45 · see citing works
Self-citationExcitotoxic neurodegeneration in Alzheimer disease
Xu, J., & Qian, C. (2000) · Zhongguo shenjing kexue zazhi · Cited by 41 · see citing works
Kauffman, M. A., Consalvo, D., Morón, D. G., Lereis, V. P., & Kochen, S. S. (2010) · Epilepsy Research · doi:10.1016/j.eplepsyres.2010.05.007 · Cited by 40 · see citing works
Glasscock, E., Qian, J., Kole, M. J., et al. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.235606 · Cited by 34 · see citing works
Cheruvallath, Z. S., Kumar, R. K., Rentel, C., Cole, D. L., & Ravikumar, V. T. (2003) · Nucleosides Nucleotides & Nucleic Acids · doi:10.1081/ncn-120022050 · Cited by 25 · see citing works
A Tau antisense oligonucleotide decreases neurone sensitivity to excitotoxic injury
Pizzi, M., Valerio, A., Ribola, M., et al. (1993) · Neuroreport · doi:10.1097/00001756-199306000-00057 · Cited by 19 · see citing works
Predicting the risk of poststroke epilepsy—why and how?
Kwan, J. S. K. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.140 · Cited by 17 · see citing works
Oka, M., Hasegawa, S., Matsushige, T., et al. (2013) · Brain and Development · doi:10.1016/j.braindev.2012.11.013 · Cited by 14 · see citing works
The Apolipoprotein E Epsilon (∊) 4 Allele is Important for Trauma-Related Epilepsy
Harden, C. L. (2004) · Epiliepsy currents/Epilepsy currents · doi:10.1111/j.1535-7597.2004.04112.x · Cited by 8 · see citing works
Are Genes the Product of Crossing-Over?
Holmes, S. (1933) · Science · doi:10.1126/science.78.2023.309 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Bang, J., Spina, S., & Miller, B. L. (2015) · The Lancet · doi:10.1016/s0140-6736(15)00461-4 · Cited by 1,144 · see citing works
Network abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022 · see citing works
Epileptic activity in Alzheimer’s disease: Causes and clinical relevance
Vossel, K. A., Tartaglia, M. C., Nygaard, H. B., Zeman, A. Z., & Miller, B. L. (2017) · The Lancet Neurology · doi:10.1016/s1474-4422(17)30044-3 · Cited by 590 · see citing works
Tau Kinetics in Neurons and the Human Central Nervous System
Sato, C., Barthélemy, N. R., Mawuenyega, K. G., Patterson, B. W., Gordon, B. A., Jockel-Balsarotti, J., Sullivan, M., Crisp, M. J., Kasten, T., Kirmess, K. M., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.015 · Cited by 586 · see citing works
Self-citationTau biomarkers in Alzheimer's disease: towards implementation in clinical practice and trials
Ossenkoppele, R., van der Kant, R., & Hansson, O. (2022) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00168-5 · Cited by 557 · 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
Self-citationUpdate on Alzheimer’s Disease Therapy and Prevention Strategies
Graham, W. V., Bonito-Oliva, A., & Sakmar, T. P. (2017) · Annual Review of Medicine · doi:10.1146/annurev-med-042915-103753 · Cited by 506 · see citing works
Morris, M., Knudsen, G. M., Maeda, S., Trinidad, J. C., Ioanoviciu, A., Burlingame, A. L., & Mucke, L. (2015) · Nature Neuroscience · doi:10.1038/nn.4067 · Cited by 472 · see citing works
Wang, C., Ward, M. E., Chen, R., Liu, K., Tracy, T. E., Chen, X., Xie, M., Sohn, P. D., Ludwig, C., Meyer-Franke, A., et al. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.08.019 · Cited by 400 · see citing works
Tau association with synaptic vesicles causes presynaptic dysfunction
Zhou, L., McInnes, J., Wierda, K., Holt, M., Herrmann, A. G., Jackson, R. J., Wang, Y.-C., Swerts, J., Beyens, J., Miskiewicz, K., et al. (2017) · Nature Communications · doi:10.1038/ncomms15295 · Cited by 434 · 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
Antisense Oligonucleotide Therapies for Neurodegenerative Diseases
Bennett, C. F., Krainer, A. R., & Cleveland, D. W. (2019) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-070918-050501 · Cited by 353 · see citing works
Self-citationMummery, C. J., Börjesson-Hanson, A., Blackburn, D. J., Vijverberg, E. G. B., De Deyn, P. P., Ducharme, S., Jonsson, M., Schneider, A., Rinne, J. O., Ludolph, A. C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02326-3 · Cited by 347 · see citing works
Self-citationDendritic Tau in Alzheimer’s Disease
Ittner, A., & Ittner, L. M. (2018) · Neuron · doi:10.1016/j.neuron.2018.06.003 · Cited by 278 · see citing works
Tau-based therapies in neurodegeneration: opportunities and challenges
Li, C., & Götz, J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.155 · Cited by 272 · see citing works
Molecular Pathogenesis of the Tauopathies
Götz, J., Halliday, G., & Nisbet, R. M. (2019) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathmechdis-012418-012936 · Cited by 276 · see citing works
Antisense oligonucleotides extend survival and reverse decrement in muscle response in ALS models
McCampbell, A., Cole, T., Wegener, A. J., Tomassy, G. S., Setnicka, A., Farley, B. J., Schoch, K. M., Hoye, M. L., Shabsovich, M., Sun, L., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99081 · Cited by 279 · see citing works
Self-citationAntisense oligonucleotides: translation from mouse models to human neurodegenerative diseases
Schoch, K. M., & Miller, T. M. (2017) · Neuron · doi:10.1016/j.neuron.2017.04.010 · Cited by 274 · see citing works
Self-citationTau: Enabler of diverse brain disorders and target of rapidly evolving therapeutic strategies
Chang, C.-W., Shao, E., & Mucke, L. (2021) · Science · doi:10.1126/science.abb8255 · Cited by 263 · see citing works
Tau in neurodegenerative disease
Gao, Y.-L., Wang, N., Sun, F.-R., Cao, X.-P., Zhang, W., & Yu, J.-T. (2018) · Annals of Translational Medicine · doi:10.21037/atm.2018.04.23 · Cited by 222 · see citing works
Human secreted tau increases amyloid-beta production
Bright, J., Hussain, S., Dang, V., Wright, S., Cooper, B., Byun, T., Ramos, C., Singh, A., Parry, G., Stagliano, N., et al. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.007 · Cited by 230 · see citing works
Ma, F., Yang, L., Sun, Z., Chen, J., Rui, X., Glass, Z., & Xu, Q. (2020) · Science Advances · doi:10.1126/sciadv.abb4429 · Cited by 218 · see citing works
“The sequence of Tau-ASO was chosen according to the published literature ( 31 ) and was synthesized by Integrated DNA Technologies (IDT).”
Tau Protein Interaction Partners and Their Roles in Alzheimer’s Disease and Other Tauopathies
Sinsky, J., Pichlerova, K., & Hanes, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179207 · Cited by 220 · see citing works
Increased 4R-Tau Induces Pathological Changes in a Human-Tau Mouse Model
Schoch, K. M., DeVos, S. L., Miller, R. L., Chun, S. J., Norrbom, M., Wozniak, D. F., Dawson, H. N., Bennett, C. F., Rigo, F., & Miller, T. M. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.042 · Cited by 175 · see citing works
Self-citationTau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β
Vossel, K. A., Xu, J. C., Fomenko, V., Miyamoto, T., Suberbielle, E., Knox, J. A., Ho, K., Kim, D. H., Yu, G.-Q., & Mucke, L. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201407065 · Cited by 167 · see citing works
Pathogenic Tau Impairs Axon Initial Segment Plasticity and Excitability Homeostasis
Sohn, P. D., Huang, C. T.-L., Yan, R., Fan, L., Tracy, T. E., Camargo, C. M., Montgomery, K. M., Arhar, T., Mok, S.-A., Freilich, R., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.08.008 · Cited by 148 · see citing works
Harris, S. S., Wolf, F., De Strooper, B., & Busche, M. A. (2020) · Neuron · doi:10.1016/j.neuron.2020.06.005 · Cited by 161 · see citing works
GSK3β and tau protein in Alzheimer's disease and epilepsy
Toral-Rios, D., Pichardo-Rojas, P. S., Alonso-Vanegas, M., & Campos-Peña, V. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00019 · Cited by 158 · see citing works
Gourmaud, S., Shou, H., Irwin, D. J., Sansalone, K., Jacobs, L. M., Lucas, T. H., Marsh, E. D., Davis, K. A., Jensen, F. E., & Talos, D. M. (2020) · Brain · doi:10.1093/brain/awz381 · Cited by 155 · see citing works
Puvenna, V., Engeler, M., Banjara, M., Brennan, C., Schreiber, P., Dadas, A., Bahrami, A., Solanki, J., Bandyopadhyay, A., Morris, J. K., et al. (2016) · Brain Research · doi:10.1016/j.brainres.2015.11.007 · Cited by 144 · see citing works
Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity
Wegmann, S., Maury, E. A., Kirk, M. J., Saqran, L., Roe, A., DeVos, S. L., Nicholls, S., Fan, Z., Takeda, S., Cagsal‐Getkin, O., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201592748 · Cited by 132 · see citing works
Self-citationAntisense drugs make sense for neurological diseases
Bennett, C. F., Kordasiewicz, H. B., & Cleveland, D. W. (2021) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023738 · Cited by 108 · see citing works
Self-citationTau reduction in the presence of amyloid-β prevents tau pathology and neuronal death in vivo
DeVos, S. L., Corjuc, B. T., Commins, C., Dujardin, S., Bannon, R. N., Corjuc, D., Moore, B. D., Bennett, R. E., Jorfi, M., Gonzales, J. A., et al. (2018) · Brain · doi:10.1093/brain/awy117 · Cited by 106 · see citing works
Self-citationCheng, J. S., Craft, R., Yu, G.-Q., Ho, K., Wang, X., Mohan, G., Mangnitsky, S., Ponnusamy, R., & Mucke, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0115765 · Cited by 100 · see citing works
Targeting tau: clinical trials and novel therapeutic approaches
VandeVrede, L., Boxer, A. L., & Polydoro, M. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.134919 · Cited by 90 · see citing works
Persistent repression of tau in the brain using engineered zinc finger protein transcription factors
Wegmann, S., DeVos, S. L., Zeitler, B., Marlen, K., Bennett, R. E., Perez-Rando, M., MacKenzie, D., Yu, Q., Commins, C., Bannon, R. N., et al. (2021) · Science Advances · doi:10.1126/sciadv.abe1611 · Cited by 77 · see citing works
Self-citationSeizure resistance without parkinsonism in aged mice after tau reduction
Li, Z., Hall, A. M., Kelinske, M., & Roberson, E. D. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.05.001 · Cited by 71 · see citing works
Tau-induced pathology in epilepsy and dementia: notions from patients and animal models.
Sánchez, M., García-Cabrero, A., Sánchez-Elexpuru, G., Burgos, D., & Serratosa, J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041092 · Cited by 68 · see citing works
Network dysfunction in<i>α</i>‐synuclein transgenic mice and human Lewy body dementia
Morris, M., Sanchez, P. E., Verret, L., Beagle, A. J., Guo, W., Dubal, D., Ranasinghe, K. G., Koyama, A., Ho, K., Yu, G., et al. (2015) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.257 · Cited by 61 · see citing works
Tau-targeting therapy in Alzheimer’s disease: Critical advances and future opportunities
Guo, Y., Li, S., Zeng, L.-H., & Tan, J. (2022) · Ageing and Neurodegenerative Diseases · doi:10.20517/and.2022.16 · Cited by 61 · see citing works
Intraventricular Delivery of siRNA Nanoparticles to the Central Nervous System
Shyam, R., Ren, Y., Lee, J., Braunstein, K. E., Mao, H.-Q., & Wong, P. C. (2015) · Molecular Therapy - Nucleic Acids · doi:10.1038/mtna.2015.15 · Cited by 58 · see citing works
Mechanisms of tau and Aβ-induced excitotoxicity
Pallo, S. P., DiMaio, J., Cook, A., Nilsson, B., & Johnson, G. V. W. (2016) · Brain Research · doi:10.1016/j.brainres.2015.12.048 · Cited by 46 · see citing works
Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms
Hwang, K., Vaknalli, R. N., Addo-Osafo, K., Vicente, M., & Vossel, K. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.903973 · Cited by 35 · see citing works
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 · see citing works
Retromer dysfunction at the nexus of tauopathies
Carosi, J. M., Denton, D., Kumar, S., & Sargeant, T. J. (2021) · Cell Death & Differentiation · doi:10.1038/s41418-020-00727-2 · Cited by 16 · see citing works
- Authors
- DeVos, S. L., Goncharoff, D. K., Chen, G., Kebodeaux, C. S., Yamada, K., Stewart, F. R., Schuler, D. R., Maloney, S. E., Wozniak, D. F., Rigo, F., Bennett, C. F., Cirrito, J. R., Holtzman, D. M., & Miller, T. M.
- Affiliations
- Washington University in St. Louis (US)
- Hope Center for Neurological Disorders (US)
- Ionis Pharmaceuticals (United States) (US)
- ORCID
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-07-31
- Volume
- 33
- Issue
- 31
- Pages
- 12887-12897
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3728694
- OpenAlex
- W2030317956
- Cited by
- 311
- References
- 86
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 22 · 2023: 27 · 2022: 24 · 2021: 36 · 2020: 34 · 2019: 29 · 2018: 25 · 2017: 22 · 2016: 16 · 2015: 24 · 2014: 19 · 2013: 1
- FWCI
- 14.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- Hope Center for Neurological Disorders (P30 NS057105)
- National Institutes of Health
- National Institute on Aging (R21AG044719, R01AG042513, P50AG005681)
- National Institute of Neurological Disorders and Stroke (P30NS057105, NS057105, K08NS074194, R01NS078398)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- tau protein, antisense oligonucleotides, neuronal hyperexcitability, seizure susceptibility, epilepsy, Alzheimer's disease, neurofibrillary tangles, network excitability, chemically induced seizures
- MeSH terms
- Age Factors, Animals, Anticonvulsants, Central Nervous System, Convulsants, Disease Models, Animal, Gene Expression Regulation, Locomotion, Mice, Inbred C57BL, Pentylenetetrazole, Picrotoxin, Seizures, Oligonucleotides, Antisense, tau Proteins, Microdialysis, Mice, Knockout, Maze Learning, Lactic Acid, Gait Disorders, Neurologic, Mice, Infusions, Intraventricular
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
