Tau-targeting antisense oligonucleotide MAPTRx in mild Alzheimer’s disease: a phase 1b, randomized, placebo-controlled trial
Open accessAbstract
Abstract Tau plays a key role in Alzheimer’s disease (AD) pathophysiology, and accumulating evidence suggests that lowering tau may reduce this pathology. We sought to inhibit MAPT expression with a tau-targeting antisense oligonucleotide (MAPT Rx ) and reduce tau levels in patients with mild AD. A randomized, double-blind, placebo-controlled, multiple-ascending dose phase 1b trial evaluated the safety, pharmacokinetics and target engagement of MAPT Rx . Four ascending dose cohorts were enrolled sequentially and randomized 3:1 to intrathecal bolus administrations of MAPT Rx or placebo every 4 or 12 weeks during the 13-week treatment period, followed by a 23 week post-treatment period. The primary endpoint was safety. The secondary endpoint was MAPT Rx pharmacokinetics in cerebrospinal fluid (CSF). The prespecified key exploratory outcome was CSF total-tau protein concentration. Forty-six patients enrolled in the trial, of whom 34 were randomized to MAPT Rx and 12 to placebo. Adverse events were reported in 94% of MAPT Rx -treated patients and 75% of placebo-treated patients; all were mild or moderate. No serious adverse events were reported in MAPT Rx -treated patients. Dose-dependent reduction in the CSF total-tau concentration was observed with greater than 50% mean reduction from baseline at 24 weeks post-last dose in the 60 mg (four doses) and 115 mg (two doses) MAPT Rx groups. Clinicaltrials.gov registration number: NCT03186989 .
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?
Tau is important in axonal stability.
“Of note, the Mapt (microtubule‐associated protein tau) gene that encodes tau, which is important in axonal stability, 20 was increased in its expression in 5XFAD/MR1 KO mice (Figure 3B).”
From The MR1/MAIT cell axis enhances dystrophic neurite development in Alzheimer's disease (2025) · cites this paper as [20]
MAPTRx is an antisense oligonucleotide drug that degrades the mRNA of the MAPT gene.
“Catherine J. Mummer’s research team used MAPTRx, an antisense oligonucleotide (ASO) drug that degrades the mRNA of the MAPT gene (which encodes the tau protein).”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [204]
Patients with mild AD treated with high doses of MAPTRx had an average reduction in tau concentrations in the CSF of more than 50 percent 24 weeks after the last dose.
“They found that patients with mild AD who were treated with high doses of MAPTRx had an average reduction in tau concentrations in the CSF of more than 50 percent 24 weeks after the last dose of the drug.”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [204]
This was the first clinical attempt to use a gene-silencing-based drug for a dementia-related disease such as AD.
“This was the first clinical attempt to use a gene-silencing-based drug for a dementia-related disease such as AD [204].”
From Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review (2024) · cites this paper as [204]
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
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · see citing works
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,010 · see citing works
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589 · see citing works
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,803 · see citing works
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,003 · see citing works
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.005 · Cited by 18,657 · see citing works
NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.03.008 · Cited by 10,152 · see citing works
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · see citing works
Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Leng, F., & Edison, P. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-020-00435-y · Cited by 3,179 · see citing works
Lane, C. A., Hardy, J., & Schott, J. M. (2018) · European Journal of Neurology · doi:10.1111/ene.13439 · Cited by 2,616 · see citing works
2020 Alzheimer's disease facts and figures
(2020) · Alzheimer's & Dementia · doi:10.1002/alz.12068 · Cited by 2,353 · see citing works
2021 Alzheimer's disease facts and figures
Anonymous (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12328 · Cited by 2,236 · see citing works
Stages of the Pathologic Process in Alzheimer Disease: Age Categories From 1 to 100 Years
Braak, H., Thal, D. R., Ghebremedhin, E., & Del Tredici, K. (2011) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e318232a379 · Cited by 2,194 · see citing works
Two Phase 3 Trials of Bapineuzumab in Mild-to-Moderate Alzheimer's Disease
Salloway, S., Sperling, R., Fox, N. C., Blennow, K., Klunk, W., Raskind, M., Sabbagh, M., Honig, L. S., Porsteinsson, A. P., Ferris, S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1304839 · Cited by 1,960 · see citing works
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892 · see citing works
Dendritic Function of Tau Mediates Amyloid-β Toxicity in Alzheimer's Disease Mouse Models
Ittner, L. M., Ke, Y. D., Delerue, F., Bi, M., Gladbach, A., van Eersel, J., Wölfing, H., Chieng, B. C., Christie, M. J., Napier, I. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.06.036 · Cited by 1,821 · see citing works
Phase 3 Trials of Solanezumab for Mild-to-Moderate Alzheimer's Disease
Doody, R. S., Thomas, R. G., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., Raman, R., Sun, X., Aisen, P. S., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1312889 · Cited by 1,668 · 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-citationDifferential Regulation of Dynein and Kinesin Motor Proteins by Tau
Dixit, R., Ross, J. L., Goldman, Y. E., & Holzbaur, E. L. F. (2008) · Science · doi:10.1126/science.1152993 · Cited by 1,012 · see citing works
Trial of Antisense Oligonucleotide Tofersen for <i>SOD1</i> ALS
Miller, T. M., Cudkowicz, M. E., Genge, A., Shaw, P. J., Sobue, G., Bucelli, R. C., Chiò, A., Van Damme, P., Ludolph, A. C., Glass, J. D., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2204705 · Cited by 966 · see citing works
Self-citationAssociation of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study
Hanseeuw, B. J., Betensky, R. A., Jacobs, H. I. L., Schultz, A. P., Sepulcre, J., Becker, J. A., Cosio, D. M. O., Farrell, M., Quiroz, Y. T., Mormino, E. C., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.1424 · Cited by 865 · see citing works
Targeting Huntingtin Expression in Patients with Huntington’s Disease
Tabrizi, S. J., Leavitt, B. R., Landwehrmeyer, G. B., Wild, E. J., Saft, C., Barker, R. A., Blair, N. F., Craufurd, D., Priller, J., Rickards, H., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1900907 · Cited by 708 · see citing works
Self-citationTau 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
Phase 1–2 Trial of Antisense Oligonucleotide Tofersen for <i>SOD1</i> ALS
Miller, T., Cudkowicz, M., Shaw, P. J., Andersen, P. M., Atassi, N., Bucelli, R. C., Genge, A., Glass, J., Ladha, S., Ludolph, A. L., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2003715 · Cited by 565 · cited 1× · see citing works
“It is not feasible to directly quantify the reduction of MAPT mRNA or tau protein in cortical tissue in a clinical trial; however, it is possible to index PD activity with CSF protein assays 31,32 .”
Self-citationEffects of Aβ immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease
Fox, N. C., Black, R. S., Gilman, S., Rossor, M. N., Griffith, S. G., Jenkins, L., & Koller, M. (2005) · Neurology · doi:10.1212/01.wnl.0000159743.08996.99 · Cited by 550 · see citing works
Nestor, S. M., Rupsingh, R., Borrie, M., Smith, M., Accomazzi, V., Wells, J. L., Fogarty, J., Bartha, R., & Initiative, T. A. D. N. (2008) · Brain · doi:10.1093/brain/awn146 · Cited by 543 · 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 · see citing works
Inhibition of neuronal maturation in primary hippocampal neurons from tau deficient mice
Dawson, H. N., Ferreira, A., Eyster, M. V., Ghoshal, N., Binder, L. I., & Vitek, M. P. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.6.1179 · Cited by 527 · 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-citationTau 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
Clinical Dementia Rating training and reliability in multicenter studies
Morris, J. C., Ernesto, C., Schafer, K. A., Coats, M. A., Leon, S. A., Sano, M. C., Thal, L. J., & Woodbury, P. (1997) · Neurology · doi:10.1212/wnl.48.6.1508 · Cited by 376 · see citing works
Takeda, S., Wegmann, S., Cho, H., DeVos, S. L., Commins, C., Roe, A. D., Nicholls, S. B., Carlson, G. A., Pitstick, R., Nobuhara, C. K., et al. (2015) · Nature Communications · doi:10.1038/ncomms9490 · Cited by 371 · see citing works
Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer's disease patients
Siemers, E. R., Sundell, K. L., Carlson, C., Case, M., Sethuraman, G., Liu‐Seifert, H., Dowsett, S. A., Pontecorvo, M. J., Dean, R. A., & Demattos, R. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2015.06.1893 · Cited by 370 · see citing works
Tabrizi, S. J., Estevez‐Fraga, C., van Roon‐Mom, W., Flower, M. D., Scahill, R. I., Wild, E. J., Muñoz-Sanjuán, I., Sampaio, C., Rosser, A., & Leavitt, B. R. (2022) · The Lancet Neurology · doi:10.1016/s1474-4422(22)00121-1 · Cited by 339 · see citing works
Tau Protein Is Required for Amyloid β-Induced Impairment of Hippocampal Long-Term Potentiation
Shipton, O. A., Leitz, J. R., Dworzak, J., Acton, C. E. J., Tunbridge, E. M., Denk, F., Dawson, H. N., Vitek, M. P., Wade-Martins, R., Paulsen, O., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.2610-10.2011 · Cited by 315 · see citing works
Antisense Reduction of Tau in Adult Mice Protects against Seizures
DeVos, S. L., Goncharoff, D. K., Chen, G., Kebodeaux, C. S., Yamada, K., Stewart, F. R., Schuler, D. R., Maloney, S. E., Wozniak, D. F., Rigo, F., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2107-13.2013 · Cited by 311 · see citing works
Self-citationSynaptic 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
Xia, C., Makaretz, S. J., Caso, C., McGinnis, S. M., Gomperts, S. N., Sepulcre, J., Gómez‐Isla, T., Hyman, B. T., Schultz, A. P., Vasdev, N., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2016.5755 · Cited by 279 · see citing works
Antisense 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 · cited 1× · see citing works
“However, at steady state with respect to both ASO distribution and the production and elimination of tau, lowered CSF tau levels should index the reduction of newly synthesized tau 21,22,37 .”
Shaw, L. M., Arias, J., Blennow, K., Galasko, D., Molinuevo, J. L., Salloway, S., Schindler, S., Carrillo, M. C., Hendrix, J. A., Ross, A., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.07.220 · Cited by 266 · see citing works
Mechanisms of action of disease-modifying agents and brain volume changes in multiple sclerosis
Zivadinov, R., Reder, A. T., Filippi, M., Minagar, A., Stüve, O., Lassmann, H., Racke, M. K., Dwyer, M. G., Frohman, E. M., & Khan, O. (2008) · Neurology · doi:10.1212/01.wnl.0000316810.01120.05 · Cited by 260 · see citing works
A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease
Salloway, S., Sperling, R., Keren, R., Porsteinsson, A. P., van Dyck, C. H., Tariot, P. N., Gilman, S., Arnold, D., Abushakra, S., Hernandez, C., et al. (2011) · Neurology · doi:10.1212/wnl.0b013e3182309fa5 · Cited by 258 · cited 1× · see citing works
“Quantitative increases in VV have been observed in treatment groups relative to placebo in clinical studies of patients with AD 38–41 while other clinical studies of AD have not reported treatment related-increases 42–45 .”
Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation
Calafate, S., Buist, A., Miśkiewicz, K., Vijayan, V. A., Daneels, G., Strooper, B. D., de Wit, J., Verstreken, P., & Moechars, D. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.043 · Cited by 257 · see citing works
Luo, W., Liu, W., Hu, X., Hanna, M., Caravaca, A., & Paul, S. M. (2015) · Scientific Reports · doi:10.1038/srep11161 · Cited by 241 · see citing works
Tau Protects Microtubules in the Axon from Severing by Katanin
Qiang, L., Yu, W., Andreadis, A., Luo, M., & Baas, P. W. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.5392-05.2006 · Cited by 235 · 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-citationPhase 3 Trials of Solanezumab and Bapineuzumab for Alzheimer's Disease
Doody, R. S., Farlow, M. R., & Aisen, P. S. S. (2014) · New England Journal of Medicine · doi:10.1056/nejmc1402193 · Cited by 170 · see citing works
Cerebral atrophy in mild cognitive impairment and Alzheimer disease
Leung, K. K., Bartlett, J. W., Barnes, J., Manning, E. N., Sebastien Ourselin, A., Fox, N. C., & Initiative, A. D. N. (2013) · Neurology · doi:10.1212/wnl.0b013e318281ccd3 · Cited by 165 · see citing works
Leroy, 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
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.2018.04.035 · Cited by 154 · 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
Pasquier, F., Sadowsky, C., Holstein, A. R., Prince, G. L., Peng, Y., Jackson, N. M., Fox, N. C., Ketter, N., Liu, E., Ryan, J. M., et al. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-150376 · Cited by 105 · 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
Analysis of in vivo turnover of tau in a mouse model of tauopathy
Yamada, K., Patel, T. K., Hochgräfe, K., Mahan, T. E., Jiang, H., Stewart, F. R., Mandelkow, E., & Holtzman, D. M. (2015) · Molecular Neurodegeneration · doi:10.1186/s13024-015-0052-5 · Cited by 76 · see citing works
Seizure 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
Sur, C., Kost, J. T., Scott, D., Adamczuk, K., Fox, N. C., Cummings, J. L., Tariot, P. N., Aisen, P. S. S., Vellas, B. J., Voss, T., et al. (2020) · Brain · doi:10.1093/brain/awaa332 · Cited by 71 · see citing works
Sud, R., Geller, E. T., & Schellenberg, G. D. (2014) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2014.30 · Cited by 69 · see citing works
Towards a better understanding of pseudoatrophy in the brain of multiple sclerosis patients
Stefano, N. D., & Arnold, D. L. (2015) · Multiple Sclerosis Journal · doi:10.1177/1352458514564494 · Cited by 68 · see citing works
Changes in Brain Volume with Bapineuzumab in Mild to Moderate Alzheimer’s Disease
Novak, G., Fox, N. C., Clegg, S., Nielsen, C. F., Einstein, S. G., Lü, Y., Tudor, I. C., Gregg, K. M., Di, J., Collins, P. V., et al. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-150448 · Cited by 53 · see citing works
Navé, S., Doody, R. S., Boada, M., Grimmer, T., Savola, J., Delmar, P., Pauly-Evers, M., Nikolcheva, T., Czech, C., Borroni, E., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161309 · Cited by 48 · see citing works
14-3-3 proteins and protein phosphatases are not reduced in tau-deficient mice
Fujio, K., Sato, M., Uemura, T., Sato, T., Sato-Harada, R., & Harada, A. (2007) · Neuroreport · doi:10.1097/wnr.0b013e32818b2a0b · Cited by 35 · see citing works
Initiative, A. D. N., Manning, E. N., Leung, K. K., Nicholas, J. M., Malone, I. B., Cardoso, M. J., Schott, J. M., Fox, N. C., & Barnes, J. (2017) · Neuroinformatics · doi:10.1007/s12021-017-9326-0 · Cited by 19 · see citing works
Wang, X., Ghayoor, A., Novicki, A., et al. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.06.2135 · Cited by 8 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- [54]Schobel, S. A. Preliminary results from GENERATION HD1, a phase III trial of tominersen in individuals with manifest HD. In CHDI 16th Annual HD Therapeutics Conference (2021).
- [55]Viglietta, V. A Ph1b/2a study of WVE-003, an investigational allele-selective, mHTT–lowering oligonucleotide for the treatment of early manifest Huntington’s disease, and review of PRECISION-HD results. In CHDI 16th Annual HDTherapeutics Conference (2021).
Cited by
Sorted by citations
Emerging diagnostics and therapeutics for Alzheimer disease
Self, W. K., & Holtzman, D. M. (2023) · Nature Medicine · doi:10.1038/s41591-023-02505-2 · Cited by 381 · see citing works
Tau-targeting therapies for Alzheimer disease: Current status and future directions
Congdon, E. E., Ji, C., Tetlow, A. M., Jiang, Y., & Sigurdsson, E. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00883-2 · Cited by 371 · see citing works
Accelerating Alzheimer’s therapeutic development: The past and future of clinical trials
Boxer, A. L., & Sperling, R. (2023) · Cell · doi:10.1016/j.cell.2023.09.023 · Cited by 197 · see citing works
Alzheimer’s Disease: Exploring the Landscape of Cognitive Decline
Tenchov, R., Sasso, J. M., & Zhou, Q. A. (2024) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.4c00339 · Cited by 170 · see citing works
Yang, J., Zhi, W., & Wang, L. (2024) · Molecules · doi:10.3390/molecules29122812 · Cited by 63 · see citing works
“This was the first clinical attempt to use a gene-silencing-based drug for a dementia-related disease such as AD [204].”
MethodMachine learning prediction of tau‐PET in Alzheimer's disease using plasma, MRI, and clinical data
Karlsson, L., Vogel, J., Arvidsson, I., Åström, K., Strandberg, O., Seidlitz, J., Bethlehem, R. A. I., Stomrud, E., Ossenkoppele, R., Ashton, N. J., et al. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.14600 · Cited by 43 · see citing works
Jiang, Y., Uhm, H., Ip, F. C., Ouyang, L., Lo, R. M. N., Cheng, E. Y. L., Cao, X., Tan, C. M. C., Law, B. C. H., Ortiz‐Romero, P., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13676 · Cited by 36 · see citing works
The MR1/MAIT cell axis enhances dystrophic neurite development in Alzheimer's disease
Wyatt‐Johnson, S. K., Ackley, S., Warren, J., Priya, R., Wan, J., Liu, S., & Brutkiewicz, R. R. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.14480 · Cited by 4 · see citing works
“19 Of note, the Mapt (microtubule-associated protein tau) gene that encodes tau, which is important in axonal stability, 20 was increased in its expression in 5XFAD/MR1 KO mice (Figure 3B).”
InfluentialTumor-derived cystatin C enables amyloid clearance
Zambelas, J., Huang, Y., Zhao, H., & Wong, S. T. C. (2026) · Trends in Immunology · doi:10.1016/j.it.2026.02.007 · Cited by 1 · see citing works
- Authors
- Mummery, 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., Bodenschatz, R., Kordasiewicz, H., Swayze, E. E., Fitzsimmons, B., Mignon, L., Moore, K. M., Yun, C., Baumann, T., Li, D., Norris, D. A., Crean, R., Graham, D. L., Huang, E., Ratti, E., Bennett, C. F., Junge, C., & Lane, R. M.
- Affiliations
- National Hospital for Neurology and Neurosurgery (GB)
- Royal Hallamshire Hospital (GB)
- Amsterdam Neuroscience (NL)
- Douglas Mental Health University Institute (CA)
- Sahlgrenska University Hospital (SE)
- University Hospital Bonn (DE)
- University of Turku (FI)
- Universität Ulm (DE)
- Ionis Pharmaceuticals (United States) (US)
- Biogen (United States) (US)
- Corresponding author
- Mummery, Catherine J.
- ORCID
- Venue
- Nature Medicine
- Published
- 2023-04-24
- Volume
- 29
- Issue
- 6
- Pages
- 1437-1447
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC10287562
- OpenAlex
- W4366824059
- Cited by
- 347
- References
- 65
- Citations by year
- 2026: 91 · 2025: 114 · 2024: 103 · 2023: 39
- FWCI
- 61.80
- Type
- journal article
- Language
- en
- Update notices
- correction (2023-10-16)
- Open access
- hybrid
- doi.org
- Locations
- Nature Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion, cc-by)
- DZNE Pub (submittedVersion, cc-by)
- UTUPub (University of Turku) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Biogen
- Ionis Pharmaceuticals
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- antisense oligonucleotides, tau protein, Alzheimer's disease, intrathecal administration, cerebrospinal fluid tau, pharmacokinetics, target engagement, drug safety, mild Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Double-Blind Method, Humans, Oligonucleotides, Antisense, tau Proteins, Treatment Outcome
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
