The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial
Open accessAbstract
Background Leuco-methylthioninium bis(hydromethanesulfonate; LMTM), a stable reduced form of the methylthioninium moiety, acts as a selective inhibitor of tau protein aggregation both in vitro and in transgenic mouse models. Methylthioninium chloride has previously shown potential efficacy as monotherapy in patients with Alzheimer's disease. We aimed to determine whether LMTM was safe and effective in modifying disease progression in patients with mild to moderate Alzheimer's disease.Methods We did a 15-month, randomised, controlled double-blind, parallel-group trial at 115 academic centres and private research clinics in 16 countries in Europe, North America, Asia, and Russia with patients younger than 90 years with mild to moderate Alzheimer's disease. Patients concomitantly using other medicines for Alzheimer's disease were permitted to be included because we considered it infeasible not to allow their inclusion; however, patients using medicines carrying warnings of methaemoglobinaemia were excluded because the oxidised form of methylthioninium in high doses has been shown to induce this condition. We randomly assigned participants (3:3:4) to 75 mg LMTM twice a day, 125 mg LMTM twice a day, or control (4 mg LMTM twice a day to maintain blinding with respect to urine or faecal discolouration) administered as oral tablets. We did the randomisation with an interactive web response system using 600 blocks of length ten, and stratified patients by severity of disease, global region, whether they were concomitantly using Alzheimer's disease-labelled medications, and site PET capability. Participants, their study partners (generally carers), and all assessors were masked to treatment assignment throughout the study. The coprimary outcomes were progression on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and the Alzheimer's Disease Co-operative Study-Activities of Daily Living Inventory (ADCS-ADL) scales from baseline assessed at week 65 in the modified intention-to-treat population. This trial is registered with Clinicaltrials.gov (NCT01689246) and the European Union Clinical Trials Registry (2012-002866-11).Findings Between Jan 29, 2013, and June 26, 2014, we recruited and randomly assigned 891 participants to treatment (357 to control, 268 to 75 mg LMTM twice a day, and 266 to 125 mg LMTM twice a day). The prespecified primary analyses did not show any treatment benefit at either of the doses tested for the coprimary outcomes (change in ADAS-Cog score compared with control [n=354, 6·32, 95% CI 5·31-7·34]: 75 mg LMTM twice a day [n=257] -0·02, -1·60 to 1·56, p=0·9834, 125 mg LMTM twice a day [n=250] -0·43, -2·06 to 1·20, p=0·9323; change in ADCS-ADL score compared with control [-8·22, 95% CI -9·63 to -6·82]: 75 mg LMTM twice a day -0·93, -3·12 to 1·26, p=0·8659; 125 mg LMTM twice a day -0·34, -2·61 to 1·93, p=0·9479). Gastrointestinal and urinary effects were the most common adverse events with both high doses of LMTM, and the most common causes for discontinuation. Non-clinically significant dose-dependent reductions in haemoglobin concentrations were the most common laboratory abnormality. Amyloid-related imaging abnormalities were noted in less than 1% (8/885) of participants.Interpretation The primary analysis for this study was negative, and the results do not suggest benefit of LMTM as an add-on treatment for patients with mild to moderate Alzheimer's disease. Findings from a recently completed 18-month trial of patients with mild Alzheimer's disease will be reported soon.Funding TauRx Therapeutics.
Overview
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
Verification
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?
The cited source says what the claim attributes to it.
In the citing paper
“Two earlier studies (NCT01689233 and NCT01689246) conducted on participants with mild AD and mild to moderate AD, respectively, indicated that the drug demonstrated good safety and potential benefits as a monotherapy.466,467”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [467]
The cited source says what the claim attributes to it.
In the citing paper
“Clinical trials of methylene blue-derived tau inhibitors in AD have generally yielded disappointing results [47–49].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [47]
In the citing paper
“Unfortunately, in two different phase 3 trials testing LMTM in all-cause dementia and mild-to-moderate AD, there was no reduction in rate of decline of cognition or ADL compared to placebo (Gauthier et al., 2016).”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Gauthier et al., 2016
In the citing paper
“Whether LMTM at the doses administered prevented accumulation of aggregated tau or decreased existing deposits was not tested.”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Gauthier et al., 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Posner, K., Brown, G. K., Stanley, B., Brent, D. A., Yershova, K. V., Oquendo, M. A., Currier, G. W., Melvin, G. A., Greenhill, L., Shen, S., et al. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.10111704 · Cited by 5,157
(2015) · HAL · Cited by 2,238
The clinical use of structural MRI in Alzheimer disease
Frisoni, G. B., Fox, N. C., Jack, C. R., Scheltens, P., & Thompson, P. M. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2009.215 · Cited by 2,113
Self-citationTwo 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
Defeating Alzheimer's disease and other dementias: a priority for European science and society
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Cedazo-Minguez, A., Dubois, B., Edvardsson, D., Feldman, H., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00062-4 · Cited by 1,676
Self-citationPhase 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
Inestrosa, N. C., Alvarez, A. R., Pérez, C. A., Moreno, R. D., Vicente, M., Linker, C., Casanueva, O. I., Soto, C. A., & Garrido, J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80108-7 · Cited by 1,117
Wischik, C. M., Novak, M., Thøgersen, H. C., Edwards, P. C., Runswick, M. J., Jakes, R., Walker, J. E., Milstein, C., Roth, M., & Klug, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.12.4506 · Cited by 939
Self-citationThe pathological process underlying Alzheimer’s disease in individuals under thirty
Braak, H., & Del Tredici, K. (2011) · Acta Neuropathologica · doi:10.1007/s00401-010-0789-4 · Cited by 812
Maruyama, M., Shimada, H., Suhara, T., Shinotoh, H., Ji, B., Maeda, J., Zhang, M.-R., Trojanowski, J. Q., Lee, V. M.-Y., Ono, M., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.037 · Cited by 760
Cited by
Sorted by citations
Items 301–400 of 429
Guo, Q., Wu, G., Huang, F., Wei, Z. C., Wang, J., Zhang, B., Liu, R., Yang, Y., Wang, X., & Li, H. (2022) · Aging · doi:10.18632/aging.204336 · Cited by 7
“Therapeutics to reduce tau pathologies are primarily focused on tau aggregation inhibition [56] and abnormal hyperphosphorylation inhibition [57].”
BackgroundKim, S., Kim, K., Nho, K. T., Myung, W., & Won, H. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-200671 · Cited by 7
Liu, H., Zhong, H., Liu, H., & Yao, X. (2021) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26196 · Cited by 7
Davidowitz, E. J., Lopez, P., Patel, D. R., Jimenez, H., Wolin, A., Eun, J. D., Adrien, L. R., Koppel, J. L., Morgan, D., Davies, P., et al. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70025 · Cited by 6
“A small molecule tau aggregation inhibitor, hydromethylthionine mesylate, a derivative of methylene blue, was selected to dissociate tau filaments, and Phase 3 trials failed to achieve its clinical endpoints (Gauthier et al. 2016).”
Wu, J., Geng, C., Liu, L., & Tang, Y. (2025) · Medicine Plus · doi:10.1016/j.medp.2025.100112 · Cited by 8
Li, S., & Bhalla, R. (2024) · Neurochemical Research · doi:10.1007/s11064-024-04178-w · Cited by 8
“However, after dosing 891 patients with mild-to-moderate AD with 75 mg or 125 mg of LMTX or placebo twice per day for 15 months, the drug failed to show significant impact on patients’ cognition [111].”
BackgroundHagar, H. C., Fernández-Vega, V., Wang, K., Jordan, L. M. O., Shumate, J., Scampavia, L. D., Tapayan, A. S., Nguyen, H. M., Spicer, T., & Kuo, M. (2025) · SLAS DISCOVERY · doi:10.1016/j.slasd.2025.100235 · Cited by 6
Fungally Derived Isoquinoline Demonstrates Inducer-Specific Tau Aggregation Inhibition
Ingham, D. J., Blankenfeld, B. R., Chacko, S., Perera, C., Oakley, B. R., & Gamblin, T. C. (2021) · Biochemistry · doi:10.1021/acs.biochem.1c00111 · Cited by 6
Schwab, K., Lauer, D., Magbagbeolu, M., Theuring, F., Gąsiorowska, A., Zadrożny, M., Harrington, C. R., Wischik, C. M., Niewiadomska, G., & Riedel, G. (2024) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2024.110955 · Cited by 6
“…symptomatic treatment with AChEI (e.g., rivastigmine, donepezil or galant-amine) and / or the NMDA receptor antagonist memantine, while it produced significant arrest of cognitive and functional decline in subjects receiving the drug as monotherapy (Gauthier et al., 2016; Wilcock et al., 2018).”
BackgroundSelf-citationEmerging drugs for progressive supranuclear palsy
Giagkou, N., & Stamelou, M. (2019) · Expert Opinion on Emerging Drugs · doi:10.1080/14728214.2019.1609450 · Cited by 6
Future Treatment of Alzheimer Disease
Keskin, A. O., Durmaz, N., Uncu, G., Erzurumluoglu, E., Yıldırım, Z., Tuncer, N., & Adapınar, D. Ö. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.85096 · Cited by 6
Screening for Core Genes Related to Pathogenesis of Alzheimer’s Disease
Yang, L.-X., Qin, Y. H., & Jian, C. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.668738 · Cited by 7
“Neurofibrillary tangles are another pathological feature of AD patients, besides, phosphorylated tau aggregates proteins to cause neuron damage, and drugs targeting tau are promising for AD therapy (Brier et al., 2016; Gauthier et al., 2016; Li and Gotz, 2017; Novak et al., 2017).”
BackgroundGauthier, S. G. (2016) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1268054 · Cited by 6
Self-citationLiu, Y., Chen, S., Li, S., Pei, Z., Fan, S., & Guo, Y. (2025) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823251362444 · Cited by 6
Deng, Y., Dong, J., Pan, C., Deng, L., He, Z., Yang, L., Hua, J., & Zhang, J. (2025) · Journal of Clinical Anesthesia · doi:10.1016/j.jclinane.2025.112060 · Cited by 6
Mitochondrial Effects of Hydromethylthionine, Rivastigmine and Memantine in Tau-Transgenic Mice
Kondak, C., Leith, M., Baddeley, T. C., Santos, R. X., Harrington, C. R., Wischik, C. M., Riedel, G., & Klein, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310810 · Cited by 5
“There were no differences between high and low doses in either of the two trials [20,21].”
ResultInfluentialSelf-citationSchwab, K., Robinson, L., Annschuetz, A., Dreesen, E., Magbagbeolu, M., Melis, V., Theuring, F., Harrington, C. R., Wischik, C. M., & Riedel, G. (2024) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2024.111172 · Cited by 4
“However, this efficacy is not seen with subjects who have already been receiving symptomatic treatments (Baddeley et al., 2015; Gauthier et al., 2016; Wilcock et al., 2018; Schelter et al., 2019; Shiells et al., 2020).”
Self-citationNovel therapeutic approaches for targeting Alzheimer’s disease
Khodakiya, A., Chaudhary, S., Chaudhary, A., & Prajapati, B. G. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13205-6.00020-0 · Cited by 5
Kang, D. M., Lukianenko, N., Baik, J., Kim, Y. K., & Lim, S. (2025) · ChemBioChem · doi:10.1002/cbic.202500316 · Cited by 4
Zhang, W., Ling, F., Qi, J., Wang, L., Qiao, Y., Zhang, Q., Qiu, X., Li, C., & Zhang, Y. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000002981 · Cited by 4
“Inspired by the recent use of MB and its derivatives in the treatment of Alzheimer’s disease [ 25 , 26 ] , MB was used off-label in this investigation to prevent POD.”
Design and application of a Tau seed amplification assay for screening inhibitors of Tau seeding
Gorski, D., Evans, H., Allison, T., Barria, C., Harrison, D., Banerjee, V., Méndez, N., Shahnawaz, M., Kaalund, S. S., Folke, J., et al. (2025) · Alzheimer s Research & Therapy · doi:10.1186/s13195-025-01855-y · Cited by 5
“Phase III trials of another compound, the methylene blue derivative LMTX, did not reach primary efficacy outcomes [33], although later reports claimed the treatment was effective in a smaller subset of enrolled patients [34].”
Mandal, P., Trushina, E. V., Arnold, M., Kaddurah‐Daouk, R., & Baloni, P. (2026) · Communications Biology · doi:10.1038/s42003-026-10474-8 · Cited by 5
Huang, Y., Chan, H., Khoo, J.-Y., Chan, M.-L., Bender, D. A., Ponnusamy, V. K., Belaidi, A. A., & Ke, L. (2025) · Neurochemistry International · doi:10.1016/j.neuint.2025.106104 · Cited by 4
Robinson, L., Bray, J. G., Melis, V., Harrington, C. R., Wischik, C. M., & Riedel, G. (2025) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000865 · Cited by 5
“By contrast, cholinesterase inhibitors (ChEIs) including rivastigmine, galantamine, and donepezil, can reverse these deficits by preventing acetylcholine (ACh) metabolism in the synaptic cleft and thus a run-down of cholinergic levels (Kondak et al ., 2021).”
Self-citationHippocampal Subregions Volume and Texture for the Diagnosis of Mild Cognitive Impairment
Chu, T., Liu, Y., Gui, B., Zhang, Z., Zhang, G., Dong, F., Dong, J., & Lin, S. (2024) · Experimental Aging Research · doi:10.1080/0361073x.2024.2313940 · Cited by 4
“The incidence of dementia is rapidly increasing worldwide (Gauthier et al., 2016).”
Xu, X., Ghosh, D., Luo, S., & Database, F. T. C. I. P. (2025) · Statistics in Biopharmaceutical Research · doi:10.1080/19466315.2025.2458018 · Cited by 4
“…all endpoints for treatment efficacy assertion, adopted in studies such as Semagacestat (Doody et al. 2013), EXPEDI-TION (Doody et al. 2014), LMTM (Gauthier et al. 2016), and ADMET 2 (Mintzer et al. 2021), or multiple endpoint strategy, requiring at least one significant outcome after multiple…”
Tripathi, S. M., McNeil, C. J., Staff, R. T., Murray, A. D., Wischik, C. M., Schelter, B. O., & Waiter, G. D. (2025) · Nuclear Medicine and Molecular Imaging · doi:10.1007/s13139-025-00908-2 · Cited by 4
“Details of clinical trial approval and methods have been described in previous publications [16–18].”
Self-citationChi, H., Sang, T., & Chang, H.-Y. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.73198 · Cited by 5
“Unfortunately, the drug did not work in phase 3 as it failed to slow cognitive decline in AD patients [155].”
BackgroundLi, C., Liu, K., Zhu, J., & Zhu, F. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00366-4 · Cited by 6
“However, clinical treatment trials including designed to test the effects of inhibiting Aβ1-42 production by β-secretase inhibitor, clearing Aβ1-42 by monoclonal antibodies, and inhibiting p-Tau by leuco-methylthioninium bis (hydromethanesulfonate; LMTM), have all failed to demonstrate clinical efficiency [1, 6, 7].”
BackgroundLee, J. H., Yoon, H. Y., Lee, H., Kang, D. M., Bak, Y., Biazruchka, I., Lim, S., Kim, S., Kim, Y. K., Kim, D., et al. (2023) · Chemistry - A European Journal · doi:10.1002/chem.202302916 · Cited by 4
Kazkayası, İ., & Telli, G. (2024) · Biology Bulletin · doi:10.1134/s106235902360455x · Cited by 4
Pragmatic Trials and Repurposed Drugs for Alzheimer Disease
Schneider, L. S. S. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.3784 · Cited by 5
Self-citationIn Vitro and In Vivo Evaluation of Small-Molecule Disassemblers of Pathological Tau Fibrils
Pan, H., Cheng, X., Zhang, J., Hou, K., Murray, K. A., Manglani, K., Zhu, C., Hsu, H., Mekkittikul, M., Halladay, T., et al. (2026) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.5c00940 · Cited by 3
Clinical Trial Development in Frontotemporal Lobar Degeneration
Ljubenkov, P. A., & Boxer, A. L. (2022) · Cambridge University Press eBooks · doi:10.1017/9781108975759.019 · Cited by 3
Niazi, S. K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251810211 · Cited by 3
Mishra, A. K., Srivastava, A., Raj, V., Saini, V., Khan, G., Singh, H., Mishra, A., & Paliwal, S. (2024) · Current Alzheimer Research · doi:10.2174/0115672050361294241211071813 · Cited by 3
Hydromethylthionine sustains truncated tau‐dependent inflammation‐lowering effects in mouse brain
Santos, R. X., Lee, S. H., Lofthouse, R. A., Melis, V., Robinson, L., Leith, M., Dreesen, E., Armstrong, P., Vorley, T., Goatman, E. A., et al. (2025) · FEBS Journal · doi:10.1111/febs.70021 · Cited by 3
Self-citationComprehending Alzheimer's Disease: Molecular Mechanisms and Treatment Strategies
Rathee, S., Pandey, V., Soni, S., Sen, D., & Jain, S. (2025) · Current Alzheimer Research · doi:10.2174/0115672050368798250626075628 · Cited by 6
Mitochondrial Dysfunction in Neurodegenerative Diseases
Chen, C., Zhao, Y., Wang, J., Pan, D., Wang, X., Xu, Y., Yan, J., Wang, L., Yang, X., Lu, M., et al. (2025) · MedComm · doi:10.1002/mco2.70326 · Cited by 3
Discovery of small molecules for the treatment of Alzheimer’s disease
Rao, P. P. N., Pham, A. T., & Shakeri, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818349-6.00011-x · Cited by 3
The Role of Oxytocin in Social Circuits and Social Behavior in Dementia
Piguet, O., Ahmed, R. M., & Kumfor, F. (2021) · Methods in molecular biology · doi:10.1007/978-1-0716-1759-5_5 · Cited by 3
Tau Pathology in Neurodegenerative Diseases
Vogels, T., & Hromádka, T. (2021) · Neuromethods · doi:10.1007/978-1-0716-1712-0_4 · Cited by 2
Thiamine pyrophosphokinase deficiency induces Alzheimer’s pathologyPreprint
Sang, S., Qian, T., Cai, F., Qiu, H., Xu, Y., Zhang, Y., Zhang, Q., Huang, S., Jiang, D., Wu, Y., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.09.141358 · Cited by 4
Decoding physical environment's role in protein phase transition
Ge, W., & Yin, D. (2025) · Advances in Colloid and Interface Science · doi:10.1016/j.cis.2025.103643 · Cited by 2
Advances in Diagnostics and Treatments for Alzheimer’s Disease
Sunderland, A., Thatcher, A. L., Rackley, E. V., & Kuruvilla, T. (2025) · British Journal of Hospital Medicine · doi:10.12968/hmed.2025.0492 · Cited by 4
Amyloid-β and Mitochondrial Membranes: A Missing Link in Alzheimer’s Pathogenesis
Houfkova, A., & Schmidt, M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05786-z · Cited by 2
Clinical Trials and Outcomes in Anti-inflammatory Therapies
Shukla, S. P., Kumar, V., Singh, S., Dwivedi, A., & Tripathi, A. (2024) · Springer eBooks · doi:10.1007/978-981-97-0157-5_12 · Cited by 2
“Current and emerging drug therapies in Alzheimer’s disease: A pathophysiological Perspective”
Aparajita, A., Jain, U., & Srivastava, P. (2024) · Neuroscience · doi:10.1016/j.neuroscience.2024.11.078 · Cited by 2
In search of Alzheimer’s disease treatment methods: trends of clinical trials
Pakulaite-Kazliene, G., Regelskytė, V., Audronytė, E., Kuzmickienė, J., & Kaubrys, G. (2018) · Neurologijos seminarai · doi:10.29014/ns.2018.03 · Cited by 1
Clinical Meaningfulness of Biomarker Endpoints in Alzheimer’s Disease Research
Ng, K. P., Pascoal, T. A., Li, X., Rosa‐Neto, P., & Gauthier, S. G. (2018) · Neuromethods · doi:10.1007/978-1-4939-7674-4_16 · Cited by 2
Self-citationBentham, P., Staff, R. T., Schelter, B. O., Shiells, H., Harrington, C. R., & Wischik, C. M. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210390 · Cited by 2
“tics for treatment of AD [11, 12] and behavioral”
BackgroundSelf-citationTau Pathology and Neurodegenerative Disorders
Takashima, A., Soeda, Y., Koike, R., & Maeda, S. (2022) · Springer eBooks · doi:10.1007/978-981-16-7977-3_22 · Cited by 2
Therapeutic approaches in proteinopathies
Nabi‐Afjadi, M., Dabirmanesh, B., & Uversky, V. N. (2024) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2024.03.008 · Cited by 2
Brain Energy Improvement as an Emerging Approach for Alzheimer’s Disease Treatment
Pan, X., Sang, S., & Zhong, C. (2021) · Neuroscience Bulletin · doi:10.1007/s12264-021-00679-8 · Cited by 2
“Inhibiting Tau aggregation has little effect on AD progression [2].”
BackgroundNeuroprotektive Therapien bei Tauopathien
Respondek, G., Krey, L., Huber, M. K., Pflugrad, H., Wegner, F., & Höglinger, G. U. (2021) · Der Nervenarzt · doi:10.1007/s00115-021-01210-0 · Cited by 3
Pharmacotherapy for Alzheimer’s disease: a perspective on treatment strategies in Japan
Nagata, T., Nakajima, S., Shinagawa, S., Noda, Y., & Mimura, M. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1502271 · Cited by 2
Drug Discovery from Medicinal Plants against Alzheimer's Disease
Marzouk, M. M., Farid, M. M., Hegazi, N. M., & Ezzat, S. M. (2023) · Wiley eBooks · doi:10.1002/9781119794127.ch3 · Cited by 4
Amin, O. M., Khalifa, M. K. A., El-Fattah, M. A. A., Allam, A., Aboutaleb, A. S., & Al‐Najjar, A. H. (2025) · Pharmaceutical Development and Technology · doi:10.1080/10837450.2025.2592102 · Cited by 1
“The positive areas were quantified using the ImageJ program (Gauthier et al. 2016).”
Tripathi, S. M., Shiells, H., Waymont, J. M. J., Staff, R. T., Schelter, B. O., Bentham, P., Wischik, C. M., & Murray, A. D. (2026) · Current Alzheimer Research · doi:10.2174/0115672050399596251106033110 · Cited by 2
Self-citationJang, K.-B., Kang, D., Lee, M.-H., Lukianenko, N., Kim, Y. K., Lim, S., Kim, S., & Cho, H. J. (2026) · Scientific Reports · doi:10.1038/s41598-026-42195-7 · Cited by 1
“However, no significant reduction in functional decline has been observed in subjects with mild to moderate AD in the trials 56,57 .”
Tauopathies and its therapeutic interventions in Alzheimer’s disease
Sonawane, S. K., Rangappa, N., Chidambaram, H., & Chinnathambi, S. (2026) · Advances in pharmacology · doi:10.1016/bs.apha.2025.12.001 · Cited by 1
Setiawan, A. W., Choi, J. T., Park, S., Choi, M., Tjandrawinata, R. R., Hadinata, E., Park, M. N., Ikrar, T., Nurkolis, F., & Kim, B. (2026) · Pharmaceuticals · doi:10.3390/ph19050792 · Cited by 1
“…programme illustrates a broader principle relevant to rhizomes: metabolic and inflammatory biomarker shifts may not be sufficient unless they translate into durable cognitive/functional benefit and, ideally for tauopathy, demonstrable effects on tau biomarkers or tau PET trajectories [12,94].”
Advances in the treatment of Alzheimer’s disease
Goceroglu, R. T., & Hacımüftüoğlu, A. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1819165 · Cited by 1
“In a phase III trial (Gauthier et al., 2016) involving patients with mild to moderate AD, LMTM did not slow cognitive or functional decline.”
Pharmacists a valuable resource for patients with Alzheimer disease and their caregivers
Ryan, M. A. (2019) · Journal of the American Pharmacists Association · doi:10.1016/j.japh.2019.09.019 · Cited by 1
PHOSPHODIESTERASE (PDE) INHIBITORS IN ALZHEIMER’S DISEASE: ROLE AND CURRENT STATUS
Jadeja, K., Khambete, M., & Khan, T. A. (2022) · INDIAN DRUGS · doi:10.53879/id.59.05.12860 · Cited by 1
Drug discovery in Alzheimer’s disease by regulating autophagy
Hamano, T., & Endo, Y. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-89906-2.00002-2 · Cited by 1
Comprehensive Review on Alzheimer’s Disease: Natural Therapeutics, Gaps, and Challenges
Mishra, P. S., Mishra, R., & Kumar, A. (2024) · Central Nervous System Agents in Medicinal Chemistry · doi:10.2174/0118715249307525240614073143 · Cited by 1
Unraveling the Effects of SARS-CoV-2 on Dementia: A Comprehensive Study
Kadiri, S. K., & Tiwari, P. K. (2024) · Coronaviruses · doi:10.2174/0126667975329888241010115929 · Cited by 1
Alzheimer’s Disease: What Do We Know About It and How Can We Tackle It?
Mirpuri, B. (2022) · International journal of high school research · doi:10.36838/v4i2.13
Singh, N., MacNicol, E., Dipasquale, O., Randall, K., Lythgoe, D. J., Mazibuko, N., Simmons, C., Selvaggi, P., Stephenson, S., Turkheimer, F., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.10.507418 · Cited by 1
Another Negative Treatment Trial for Mild-to-Moderate Alzheimer Disease
Molano, J. R. V. (2016) · Journal watch · doi:10.1056/nejm-jw.na42910
Investigating the role of normal and abnormal beta-amyloid processing in cognition
Freeman, T. J. (2019) · ORCA Online Research @Cardiff (Cardiff University)
Methylenblau ohne Effekt auf Tau-Aggregate
Medizin, S. (2017) · InFo Neurologie + Psychiatrie · doi:10.1007/s15005-017-2175-4
Effects of anle138b treatment on amyloid-β neurotoxicity
Thomas, C. (2020) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-8233
Neuropsychology, social cognition, and loss of insight in frontotemporal dementia
O’Keeffe, F. M., & McCormack, D. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-818000-6.00012-3
Pathogenesis of Alzheimer’s disease and its treatments: A systematic review
Lou, Y., Sun, S., & Tan, J. (2021) · E3S Web of Conferences · doi:10.1051/e3sconf/202130802012
p38α-MAPK-deficient myeloid cells ameliorate symptoms and pathology of APP-transgenic AD micePreprint
Luo, Q., Schnöder, L., Hao, W., Litzenburger, K., Decker, Y., Tomic, I., Menger, M. D., Fassbender, K. C., & Liu, Y. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.10.18.464870
Villalobos-Nova, K., Monroy-Moya, S., Maulen-Peñaloza, J., Pinto, G. C. M., & Cornejo, A. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867329666220508175340
Meta-Analysis of Natural vs Pharmaceutical Interventions for Alzheimer's Disease
Vrublevskaya, T. (2021) · San José State University ScholarWorks (San Jose State University) · doi:10.31979/etd.b494-dcd5
Ashford, J. W. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734280398.793553881
Wu, K., Xu, C., Tian, X., Qiu, G., Liu, W., Guo, Q., Chen, C., Liu, J., Guo, Z., Chen, H., et al. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4125474
Explorando o papel dos RNAs longos não codificadores na doença de Alzheimer
Vasquez, F. J. D. A. (2022) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2022.tde-08082022-105803
Therapeutic and immunomodulatory functions of the translocator protein in Alzheimer's disease
Fairley, L. H. (2022) · DR-NTU (Nanyang Technological University) · doi:10.32657/10356/160865
Hippocampal Subregions Volume and Texture for the Diagnosis of Mild Cognitive ImpairmentPreprint
Chu, T., Liu, Y., Zhang, Z., Zhang, G., Dong, F., Dong, J., & Lin, S. (2022) · Research Square · doi:10.21203/rs.3.rs-2182063/v1
Hippocampal Subregions Volume and Texture for the Diagnosis of Mild Cognitive ImpairmentPreprint
Chu, T., Liu, Y., Zhang, Z., Zhang, G., Dong, F., Dong, J., & Lin, S. (2023) · Research Square · doi:10.21203/rs.3.rs-2182063/v2
Arastoo, M., Mazanetz, M. P., Miller, S., Shiells, H., Hull, C. E., Robinson, K. A., Storey, J. M. D., Harrington, C. R., & Wischik, C. M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241813747
“Because of the broader potential clinical utility of a specific anti-hypoxaemia drug, we undertook a preliminary investigation of the effects of HMTM treatment on SpO2 and metHb levels in patients participating in either of two Phase 3 clinical trials in AD [7,8] in which metHb and SpO2 levels were monitored routinely…”
MethodSelf-citationAsociación entre enfermedad periodontal y enfermedad de Alzheimer
García-Vásquez, A. T., Vidal-Chávez, S. R., Anccasi-Zevallos, M., Franco-Quispe, G. A., Ramos-Perfecto, D., & Mattos-Vela, M. A. (2023) · Bionatura · doi:10.21931/rb/2023.08.04.26
Manjunath, K., Kaur, A., Paramesh, D. B., & Murthy, S. (2023) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/9789815136142123010014
Methylene blue treatment on Alzheimer and inflammatory bowel disease
Öğünç, B., Ramoğlu, N., & Sakin, I. (2021) · Demiroglu Science University Florence Nightingale Journal of Medicine · doi:10.5606/fng.btd.2020.25053
“[47]”
Tau targeting biomimetic nanoparticles
Bhatt, S., Gawli, C., & Patil, C. R. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23841-3.00008-x
Taşkın, T., Mente, S., Ekentok, C., Ermanoğlu, M., Özdemir, M., Yalçın, B., & Omurtag, G. Z. (2024) · Journal of the Turkish Chemical Society Section A Chemistry · doi:10.18596/jotcsa.1499076
Pharmacotherapy of Alzheimer's disease: A thorny road to success
Ibrahim, N. H., Kumar, J., & Mohamed, W. M. Y. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15702-8.00027-0
Chan, D., Spires‐Jones, T. L., Provenzano, F. A., Glennon, E. B. C., & Duff, K. (2025) · Oxford University Press eBooks · doi:10.1093/med/9780190065324.003.0020
Wang, P., Han, X., Yu, Y., Zhou, Y., Ma, Q., Lv, P., Li, W., Zhang, J., Jiang, H., Zhang, W., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5134448
Gregory, S., Saunders, S., & Ritchie, C. W. (2025) · Elsevier eBooks · doi:10.1016/b978-0-12-822240-9.00016-8
Amyloid- and Tau-Targeted Therapies in Alzheimer’s Disease
Rajic, A. J., Galasko, D. R., & Tuszynski, M. H. (2025) · Springer eBooks · doi:10.1007/978-3-031-89307-0_17
Ye, H., Zhuang, C., Jin, Z., Hu, Y., He, J., Yu, Q., Hu, H., & Zheng, Y. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251385244
Hypothesis-Driven Insights and Clinical Trial Updates in Alzheimer’s Disease Pathogenesis
Alhawarri, M. B. (2025) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273387383250924031644
Treatment of Frontotemporal Dementias
Chen, D., VandeVrede, L. A., & Boxer, A. L. (2025) · Cambridge University Press eBooks · doi:10.1017/9781108985055.022
Metadata
- Authors
- Gauthier, S., Feldman, H. H., Schneider, L. S., Wilcock, G. K., Frisoni, G. B., Hardlund, J. H., Moebius, H. J., Bentham, P., Kook, K. A., Wischik, D. J., Schelter, B. O., Davis, C. S., Staff, R. T., Bracoud, L., Shamsi, K., Storey, J. M. D., Harrington, C. R., & Wischik, C. M.
- Affiliations
- Douglas Mental Health University Institute (CA)
- University of California San Diego (US)
- University of Southern California (US)
- University of Oxford (GB)
- University of Geneva (CH)
- TauRx (United Kingdom) (GB)
- University of Aberdeen (GB)
- Corresponding author
- Wischik, Claude M
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2016-12
- Volume
- 388
- Issue
- 10062
- Pages
- 2873-2884
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC5164296
- OpenAlex
- W2553774099
- Cited by
- 427
- References
- 31
- Citations by year
- 2026: 25 · 2025: 46 · 2024: 47 · 2023: 41 · 2022: 47 · 2021: 46 · 2020: 48 · 2019: 47 · 2018: 48 · 2017: 27 · 2016: 4
- FWCI
- 33.77
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- PubMed Central (acceptedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- TauRx Pharmaceuticals
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, tau aggregation, methylene blue, disease progression, ADAS-Cog, cognitive decline, activities of daily living, methemoglobinemia, drug safety, mild to moderate Alzheimer's disease, amyloid PET, FDG-PET
- MeSH terms
- Activities of Daily Living, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Brain, Dose-Response Relationship, Drug, Double-Blind Method, Female, Humans, Male, Middle Aged, Psychiatric Status Rating Scales, tau Proteins, Treatment Failure, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
