The DOI matches its Crossref record; 44 of the 47 references it cites were found in a registry or an index.
Alzheimer's disease drug development pipeline: 2017
Open accessAbstract
Introduction: There is an urgent need to develop new treatments for Alzheimer's disease (AD) and to understand the drug development process for new AD therapies. Methods: We assessed the agents in the AD pipeline as documented in clinicaltrials.gov for phase I, phase II, and phase III, accessed 1/5/2017. Results: There are 105 agents in the AD treatment development pipeline, of which 25 agents are in 29 trials in phase I, 52 agents are in 68 trials in phase II, and 28 agents are in 42 trials in phase III. Seventy percent of drugs in the AD pipeline are disease‐modifying therapies (DMTs). Fourteen percent are symptomatic cognitive enhancers, and 13% are symptomatic agents addressing neuropsychiatric and behavioral changes (2% have undisclosed mechanisms). Most trials are sponsored by the biopharmaceutical industry. Trials include patients with preclinical AD (cognitively normal with biomarker evidence of AD), prodromal AD (mild cognitive symptoms and biomarker evidence of AD), and AD dementia. Biomarkers are included in many drug development programs particularly those for DMTs. Thirteen of 46 phase II DMT trials have amyloid imaging as an entry criterion, and 10 of 28 phase III trials incorporate amyloid imaging for diagnosis and entry. A large number of participants are needed for AD clinical trials; in total, 54,073 participants are required for trials spanning preclinical AD to AD dementia. When compared with the 2016 pipeline, there are eight new agents in phase I, 16 in phase II, and five in phase III. Discussion: The AD drug development pipeline has 105 agents divided among phase I, phase II, and phase III. The trials include a wide range of clinical trial populations, many mechanisms of action, and require a substantial number of clinical trial participants. Biomarkers are increasingly used in patient identification and as outcome measures, particularly in trials of DMTs.
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?
In the citing paper
“A number of additional pathogenic mechanisms have been described, possibly overlapping with Aβ plaques and NFT formation or induced by them, including inflammation, oxidative damage, iron deregulation, and cholesterol metabolism blood-brain barrier (BBB) dysfunction or α-synuclein toxicity.9-13”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [12]
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
2016 Alzheimer's disease facts and figures
Alzheimer's Association (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.03.001 · Cited by 5,069
The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease
Sevigny, J., Chiao, P., Bussière, T., Weinreb, P. H., Williams, L., Maier, M., Dunstan, R., Salloway, S., Chen, T., Ling, Y., et al. (2016) · Nature · doi:10.1038/nature19323 · Cited by 3,059 · cited 1×
“Aducanumab targets multiple Ab species, has had an encouraging phase I/II trial, and is continuing in phase III [35].”
BackgroundAlzheimer’s disease drug-development pipeline: Few candidates, frequent failures
Cummings, J. L., Morstorf, T., & Zhong, K. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt269 · Cited by 1,744 · cited 1×
“Although there are promising agents in the pipeline that could achieve this goal, it is clear that given the high rate of failure of AD drug development [38], the aim of having a repertoire of agents that could respond comprehensively and individually to a patient’s clinical circumstances within the 2025 timeframe is…”
BackgroundSelf-citation2015 Alzheimer's disease facts and figures
Alzheimer's Association (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.02.003 · Cited by 1,673
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework
Cook, D., Brown, D., Alexander, R., March, R., Morgan, P., Satterthwaite, G., & Pangalos, M. N. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4309 · Cited by 1,344 · cited 1×
“Biomarkers can contribute substantially to drug development success [39].”
BackgroundClinical Trial Registration: A Statement from the International Committee of Medical Journal Editors
De Angelis, C., Drazen, J. M., Frizelle, F. A., Haug, C., Hoey, J., Horton, R., Kotzin, S., Laine, C., Marusic, A., Overbeke, A. J. P. M., et al. (2004) · New England Journal of Medicine · doi:10.1056/nejme048225 · Cited by 1,241
Sperling, R. A., Jack, C. R., Black, S. E., Frosch, M. P., Greenberg, S. M., Hyman, B. T., Scheltens, P., Carrillo, M. C., Thies, W., Bednar, M. M., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.05.2351 · Cited by 857
Lombardo, I., Ramaswamy, G., Piscitelli, S. C., & Friedhoff, L. T. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.08.154 · Cited by 656
Weiner, M. W., Veitch, D. P., Aisen, P. S. S., Beckett, L. A., Cairns, N. J., Green, R. C., Harvey, D. J., Jack, C. R., Jagust, W. J., Morris, J. C., et al. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.10.006 · Cited by 523
Drug development in Alzheimer’s disease: the path to 2025
Cummings, J., Aisen, P. S., DuBois, B., Frölich, L., Jack, C. R., Jones, R. W., Morris, J. C., Raskin, J., Dowsett, S. A., & Scheltens, P. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0207-9 · Cited by 459 · cited 3×
“This means that under current circumstances, an agent must now be in phase II to possibly be approved by 2025 [5].”
BackgroundSelf-citation
Flagged first, then by citations
3 of the 47 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Alzheimer's Association, 2015, Changing the Trajectory of Alzheimer's Disease: How a Treatment by 2025 Saves Lives and Dollars
- Tan S.B., 2009, Clinical Trials Handbook, 255
- Babic T., 2016, Improving screen fail and recruitment rates in Alzheimer's disease clinical trials, J Clin Stud, 8, 38
Cited by
Sorted by citations
Diagnosis and Management of Dementia: Review
Arvanitakis, Z., Shah, R. C., & Bennett, D. A. (2019) · JAMA · doi:10.1001/jama.2019.4782 · Cited by 1,561
Alzheimer’s disease: pathogenesis, diagnostics, and therapeutics
Tiwari, S., Atluri, V., Kaushik, A., Yndart, A., & Nair, M. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s200490 · Cited by 1,308
“Table 1 summarizes the drugs specific to amyloid that are being studied andwhich target sufficiently fundamental and proximate degenerative mechanisms.(64,65)”
BackgroundReligious Orders Study and Rush Memory and Aging Project
Bennett, D. A., Buchman, A. S., Boyle, P. A., Barnes, L. L., Wilson, R. S., & Schneider, J. A. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179939 · Cited by 1,260
“Therearecurrentlyabout100drugsintheAD pipelineintheUSAwithanadditional100indevel-opmentintheEuropeanUnionwithparticipants rangingfromthosewithmoderatetosevereAD dementiatoasymptomaticpersons[443,444].”
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138
Current and Future Treatments in Alzheimer Disease: An Update
Yiannopoulou, K. G., & Papageorgiou, S. G. (2020) · Journal of Central Nervous System Disease · doi:10.1177/1179573520907397 · Cited by 966
Global estimates on the number of persons across the Alzheimer's disease continuum
Gustavsson, A., Norton, N., Fast, T., Frölich, L., Georges, J., Holzapfel, D., Kirabali, T., Krolak‐Salmon, P., Rossini, P. M., Ferretti, M. T., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.12694 · Cited by 895
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870
“Since the systematic review conducted by Cummings and colleagues in January 2017 [393], Merck has halted its phase II and III trials of the BACE inhibitor verubescestat for lack of efficacy; a leading theory for this failure is the timing of treatment [399].”
BackgroundMethodInfluentialLópez, J. A., González, H. M., & Léger, G. C. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804766-8.00013-3 · Cited by 884
Alzheimer's disease drug development pipeline: 2019
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2019) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.05.008 · Cited by 762
Self-citationAlzheimer's disease drug development pipeline: 2018
Cummings, J., Lee, G., Ritter, A., & Zhong, K. (2018) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.03.009 · Cited by 697
“Eight agents listed in phase III in 2017 [7] failed in clinical trials as of January 30, 2018.”
BackgroundSelf-citationAlzheimer’s disease drug development pipeline: 2022
Cummings, J., Lee, G., Nahed, P., Kambar, M. E. Z. N., Zhong, K., Fonseca, J., & Taghva, K. (2022) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12295 · Cited by 665
Role of Tau as a Microtubule-Associated Protein: Structural and Functional Aspects
Barbier, P., Zejneli, O., Martinho, M., Lasorsa, A., Belle, V., Smet‐Nocca, C., Tsvetkov, P. O., Devred, F., & Landrieu, I. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00204 · Cited by 653
“Efforts for clinical intervention in the AD field have so far mainly focused on blocking the formation of extracellular amyloid β deposits, another type of aggregates observed in the brain of AD patients (Cummings et al., 2017).”
BackgroundAlzheimer’s disease drug development pipeline: 2020
Cummings, J., Lee, G., Ritter, A., Sabbagh, M., & Zhong, K. (2020) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12050 · Cited by 557
Self-citationAlzheimer’s disease drug development pipeline: 2021
Cummings, J., Lee, G., Zhong, K., Fonseca, J., & Taghva, K. (2021) · Alzheimer's & Dementia: Translational Research & Clinical Interventions · doi:10.1002/trc2.12179 · Cited by 539
Self-citationCurrent state of Alzheimer’s fluid biomarkers
Molinuevo, J. L., Ayton, S., Batrla, R., Bednar, M. M., Bittner, T., Cummings, J., Fagan, A. M., Hampel, H., Mielke, M. M., Mikulskis, A., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1932-x · Cited by 518
Self-citationInflammation: the link between comorbidities, genetics, and Alzheimer’s disease
Newcombe, E. A., Camats-Perna, J., Silva, M. L., Valmas, N., Huat, T. J., & Medeiros, R. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1313-3 · Cited by 532
Drug repositioning: a brief overview
Jourdan, J.-P., Bureau, R., Rochais, C., & Dallemagne, P. (2020) · Journal of Pharmacy and Pharmacology · doi:10.1111/jphp.13273 · Cited by 470
“In 2017, over 100 drugs were undergoing clinical trials for this disease.([19]) One-quarter (27) of these drugs have already been marketed and are therefore being investigated for potential repositioning (Table 1).”
BackgroundPerez Ortiz, J. M., & Swerdlow, R. H. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14585 · Cited by 426
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
Cano, A., Ettcheto, M., Chang, J.-H., Barroso, E., Espina, M., Kühne, B. A., Barenys, M., Auladell, C., Folch, J., Souto, E. B., et al. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.03.010 · Cited by 337
Alzheimer’s Disease: An Update and Insights Into Pathophysiology
Abubakar, M. B., Sanusi, K. O., Ugusman, A., Mohamed, W. M. Y., Kamal, H., Ibrahim, N. H., Khoo, C. S., & Kumar, J. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.742408 · Cited by 302
Multiplex proteomics identifies novel CSF and plasma biomarkers of early Alzheimer’s disease
Whelan, C. D., Mattsson, N., Nagle, M. W., Vijayaraghavan, S., Hyde, C., Janelidze, S., Stomrud, E., Lee, J., Fitz, L., Samad, T. A., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0795-2 · Cited by 262
Clinical trials of new drugs for Alzheimer disease: a 2020–2023 update
Huang, L.-K., Kuan, Y.-C., Lin, H.-W., & Hu, C.-J. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00976-6 · Cited by 252
A natural experiment on the effect of herpes zoster vaccination on dementia
Eyting, M., Xie, M., Michalik, F., Heß, S., Chung, S., & Geldsetzer, P. (2025) · Nature · doi:10.1038/s41586-025-08800-x · Cited by 273
Memantine for the Treatment of Dementia: A Review on its Current and Future Applications
Folch, J., Busquets, O., Ettcheto, M., Sánchez-López, E., Castro-Torres, R. D., Verdaguer, E., Garcia, M. L., Olloquequi, J., Casadesús, G., Beas-Zarate, C., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170672 · Cited by 245
“That is why current efforts in AD therapy are focusing on the research and development of new molecules that can modify the course of AD progression [27, 28].”
BackgroundAdvances in the development of new biomarkers for Alzheimer’s disease
Klyucherev, T. O., Olszewski, P., Shalimova, A. A., Chubarev, V. N., Tarasov, V. V., Attwood, M. M., Syvänen, S., & Schiöth, H. B. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00296-z · Cited by 241
“A recent review suggests that there are about 28 agents in phase 3, 74 in phase 2, and 30 in phase 1 clinical studies, but the failure rate due to lack of evidence of effectiveness is high [9, 10].”
BackgroundThe “rights” of precision drug development for Alzheimer’s disease
Cummings, J. L., Feldman, H., & Scheltens, P. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0529-5 · Cited by 247
Self-citationMartínez‐Losa, M., Tracy, T. E., Ma, K., Verret, L., Clemente-Perez, A., Khan, A. S., Cobos, I., Ho, K., Gan, L., Mucke, L., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.029 · Cited by 242
“Because the longterm efficacy and safety of anti-Ab treatments remains uncertain (Cummings et al., 2017), it is important to explore alternative and complementary strategies to counteract effects that mediate AD-related network dysfunction and cognitive decline.”
Towards a future where Alzheimer’s disease pathology is stopped before the onset of dementia
van der Flier, W. M., de Vugt, M. E., Smets, E. M. A., Blom, M., & Teunissen, C. E. (2023) · Nature Aging · doi:10.1038/s43587-023-00404-2 · Cited by 220
Maiti, P., & Dunbar, G. L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19061637 · Cited by 243
“Although there have been several studies using therapeutic strategies involving anti-amyloids, anti-inflammatory agents, and small molecule drugs [5], to slow or halt the progression of neurological diseases, none of them have proven effective without serious effects or abbreviated half-lives.”
BackgroundNew approaches to symptomatic treatments for Alzheimer’s disease
Cummings, J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00424-9 · Cited by 226
Self-citationPark, J.-H., Ju, Y. H., Choi, J. W., Song, H. J., Jang, B. K., Woo, J., Chun, H., Kim, H. J., Shin, S. J., Yarishkin, O., et al. (2019) · Science Advances · doi:10.1126/sciadv.aav0316 · Cited by 216
Cummings, J., Ritter, A., & Zhong, K. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179901 · Cited by 176
“small molecule agents administered orally [7, 8].”
Self-citationThe Amyloid Phenomenon and Its Significance in Biology and MedicinePreprint
Dobson, C. M., Knowles, T. P. J., & Vendruscolo, M. (2019) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033878 · Cited by 169
Highlights in BACE1 Inhibitors for Alzheimer's Disease Treatment
Coimbra, J. R. M., Marques, D., Baptista, S. J., Pereira, C., Moreira, P. I., Dinis, T. C. P., Santos, A. E., & Salvador, J. A. R. (2018) · Frontiers in Chemistry · doi:10.3389/fchem.2018.00178 · Cited by 171
Albertini, C., Salerno, A., de Sena Murteira Pinheiro, P., & Bolognesi, M. L. (2021) · Medicinal Research Reviews · doi:10.1002/med.21699 · Cited by 179
Rabinovici, G. D. (2019) · Continuum · doi:10.1212/con.0000000000000700 · Cited by 170
Chen, Y.-A., Lu, C.-H., Ke, C.-C., Chiu, S.-J., Jeng, F.-S., Chang, C.-W., Yang, B.-H., & Liu, R.-S. (2021) · Biomedicines · doi:10.3390/biomedicines9060594 · Cited by 167
“Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that accounts for 50–70% of the cases of dementia [1].”
BackgroundBenzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease
Goyal, D., Kaur, A., & Goyal, B. (2018) · ChemMedChem · doi:10.1002/cmdc.201800156 · Cited by 159
Rajasekhar, K., & Govindaraju, T. (2018) · RSC Advances · doi:10.1039/c8ra03620a · Cited by 150
Novak, P., Schmidt, R., Kontsekova, E., Kovacech, B., Smolek, T., Katina, S., Fialova, L., Prcina, M., Parrak, V., Dal-Bianco, P., et al. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0436-1 · Cited by 147
Bilingualism: Pathway to Cognitive Reserve
Bialystok, E. (2021) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2021.02.003 · Cited by 167
Imam, F. B., Saloner, R., Vogel, J. W., Krish, V. S., Abdel-Azim, G., Ali, M., An, L., Anastasi, F., Bennett, D. A. A., Binette, A. P., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03834-0 · Cited by 156
Longitudinal CSF proteomics identifies NPTX2 as a prognostic biomarker of Alzheimer's disease
Libiger, O., Shaw, L. M., Watson, M. H., Nairn, A. C., Umaña, K. L., Biarnes, M. C., Canet‐Avilés, R. M., Jack, C. R., Breton, Y., Cortes, L., et al. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12353 · Cited by 108
“The fivebiomarkers—(1) chromograninA (CMGA), (2) fatty acid binding protein (FABPH), (3) neuronal pentraxin 2 (NPTX2), (4) secretogranin (SCG2), and (5) neurosecretory protein VGF (VGF)— were selected based on evidence gathered from prior research including a cross-sectional mass spectrometry (MS)-based proteomic stud…”
Neurohealth Properties ofHericium erinaceusMycelia Enriched with Erinacines
Li, I.-C., Lee, L., Tzeng, T.-T., Chen, W.-P., Chen, Y., Shiao, Y., & Chen, C. (2018) · Behavioural Neurology · doi:10.1155/2018/5802634 · Cited by 138
“, was observed during recent times [7].”
Acetylation changes tau interactome to degrade tau in Alzheimer’s disease animal and organoid models
Choi, H., Kim, H. J., Yang, J., Chae, S., Lee, W., Chung, S., Kim, J., Choi, H., Song, H., Lee, C. K., et al. (2019) · Aging Cell · doi:10.1111/acel.13081 · Cited by 124
Alzheimer disease blood biomarkers: considerations for population-level use
Mielke, M. M., & Fowler, N. R. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00989-1 · Cited by 125
The wonderland of neuronal nicotinic acetylcholine receptors
Bertrand, D., & Terry, A. V. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.12.008 · Cited by 118
Pierzynowska, K., Podlacha, M., Gaffke, L., Majkutewicz, I., Mantej, J., Węgrzyn, A., Osiadły, M., Myślińska, D., & Węgrzyn, G. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.01.030 · Cited by 116
“AD is particularly difficult to treat, which is exemplified by a high number of approaches, studies and trials which unfortunately failed to develop an effective therapy (Cummings et al., 2017).”
The role of 5 HT6-receptor antagonists in Alzheimer’s disease: an update
Khoury, R., Grysman, N., Gold, J., Patel, K., & Grossberg, G. T. (2018) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2018.1483334 · Cited by 115
“Clinical trials of disease-modifying therapies (DMTs) have been the top priority in AD research in an attempt to find a definite treatment: 70% of drugs in the pipeline are DMTs aiming at halting or reversing AD’s progression, while only 14% are symptomatic cognitive enhancers [5].”
BackgroundKarstens, A. J., Tussing-Humphreys, L., Zhan, L., Rajendran, N., Cohen, J., Dion, C., Zhou, X. J., & Lamar, M. (2019) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy275 · Cited by 136
“85), we created High and Low self-reported MedDiet adherence groups based on the median split [dummy-coded high (1) and low (0)].”
BackgroundMethodPhospho-Tau Bar Code: Analysis of Phosphoisotypes of Tau and Its Application to Tauopathy
Kimura, T., Sharma, G., Ishiguro, K., & Hisanaga, S. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00044 · Cited by 112
“Several protein kinase inhibitors are in Phase II trials for AD in 2017 (Cummings et al., 2017).”
BackgroundThe costs of developing treatments for Alzheimer's disease: A retrospective exploration
Cummings, J. L., Goldman, D. P., Simmons‐Stern, N. R., & Ponton, E. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12450 · Cited by 111
Self-citationTau binding protein CAPON induces tau aggregation and neurodegeneration
Hashimoto, S., Matsuba, Y., Kamano, N., Mihira, N., Sahara, N., Takano, J., Muramatsu, S.-I., Saido, T. C., & Saito, T. (2019) · Nature Communications · doi:10.1038/s41467-019-10278-x · Cited by 111
Precision pharmacology for Alzheimer’s disease
Hampel, H. J., Vergallo, A., Aguilar, L. F., Benda, N., Broich, K., Cuello, A. C., Cummings, J. L., Dubois, B., Federoff, H. J., Fiandaca, M. S., et al. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2018.02.014 · Cited by 114
“All drug development programs aimed at developing disease-modifying treatments for AD or any other neurodegenerative disorder have failed [206].”
BackgroundSelf-citationRezai, A. R., Ranjan, M., Haut, M. W., Carpenter, J., D’Haese, P.-F., Mehta, R. I., Najib, U., Wang, P., Claassen, D. O., Chazen, J. L., et al. (2023) · Journal of Neurosurgery · doi:10.3171/2022.9.jns221565 · Cited by 111
Present Algorithms and Future Treatments for Alzheimer’s Disease
Grossberg, G. T., Tong, G., Burke, A. D., & Tariot, P. N. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180903 · Cited by 111
“, tyrosine kinase inhibitor, receptor for advanced glycation end-products inhibitor) are being investigated [103, 107].”
Dilmore, A. H., Martino, C., Neth, B. J., West, K., Zemlin, J., Rahman, G., Panitchpakdi, M. W., Meehan, M. J., Weldon, K. C., Blach, C., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13007 · Cited by 108
Iraji, A., Khoshneviszadeh, M., Firuzi, O., Khoshneviszadeh, M., & Edraki, N. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.103649 · Cited by 106
The price of progress: Funding and financing Alzheimer's disease drug development
Cummings, J. L., Reiber, C. L., & Kumar, P. (2018) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.04.008 · Cited by 97
Self-citationMullane, K., & Williams, M. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.09.026 · Cited by 98
Lifke, V., Kollmorgen, G., Manuilova, E., Oelschlaegel, T., Hillringhaus, L., Widmann, M., Arnim, C. A. F. V., Otto, M., Christenson, R. H., Powers, J. L., et al. (2019) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2019.05.005 · Cited by 94
Sirtuin 1 and Alzheimer's disease: An up-to-date review
Rizzi, L., & Roriz‐Cruz, M. (2018) · Neuropeptides · doi:10.1016/j.npep.2018.07.001 · Cited by 84
Moore, K. B. E., Hung, T.-J., & Fortin, J. S. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103487 · Cited by 90
Overview of tau PET molecular imaging
Petersen, G. C., Roytman, M., Chiang, G. C.-Y., Li, Y., Gordon, M. L., & Franceschi, A. M. (2022) · Current Opinion in Neurology · doi:10.1097/wco.0000000000001035 · Cited by 87
The A4 study: β ‐amyloid and cognition in 4432 cognitively unimpaired adults
Insel, P. S., Donohue, M., Sperling, R. A., Hansson, O., & Mattsson, N. (2020) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51048 · Cited by 81
“The failure of trials directed against symptomatic AD over the last few years has led to an increased interest among researchers and drug developers to study preclinical AD.(1,2) The hope is that early interventions, initiated before widespread neuronal damage, may be more likely to modify the disease course.”
BackgroundInfluentialBacterial DNA promotes Tau aggregation
Tetz, G. V., Pinho, M. A., Pritzkow, S., Méndez, N., Soto, C. A., & Tetz, V. (2020) · Scientific Reports · doi:10.1038/s41598-020-59364-x · Cited by 81
Yulug, B., Altay, O., Li, X., Hanoglu, L., Cankaya, S., Lam, S., Velioglu, H. A., Yang, H., Coskun, E., Idil, E., et al. (2023) · Translational Neurodegeneration · doi:10.1186/s40035-023-00336-2 · Cited by 79
Danis, C., Dupré, E., Zejneli, O., Caillierez, R., Arrial, A., Bégard, S., Mortelecque, J., Eddarkaoui, S., Loyens, A., Cantrelle, F., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.009 · Cited by 75
“Intervention strategies based on the amyloid cascade hypothesis had, up to date, limited success despite their being the primary target of clinical assays 2 .”
Repurposed agents in the Alzheimer’s disease drug development pipeline
Bauzon, J., Lee, G., & Cummings, J. (2020) · Alzheimer's Research & Therapy · doi:10.1186/s13195-020-00662-x · Cited by 77
Self-citationPharmacological intervention of histone deacetylase enzymes in the neurodegenerative disorders
Gupta, R. V., Ambasta, R. K., & Kumar, P. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117278 · Cited by 83
The Global Economic Impact of Neurodegenerative Diseases: Opportunities and Challenges
Zahra, W., Nand, S., Birla, H., Singh, S. S., Dilnashin, H., Rathore, A. S., & Singh, S. P. (2019) · Springer eBooks · doi:10.1007/978-981-13-9431-7_17 · Cited by 90
Quansah, E., Peelaerts, W., Langston, J. W., Simon, D. K., Colca, J. R., & Brundin, P. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0260-x · Cited by 76
“disease-modifying treatments for Alzheimer’s disease and other major neurodegenerative diseases [15].”
BackgroundGomaa, A. A., Makboul, R. M., Al-Mokhtar, M. A., & Nicola, M. A. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.10.056 · Cited by 75
Moscoso, A., Silva‐Rodríguez, J., Aldrey, J. M., Cortés, J., Fernández‐Ferreiro, A., Gómez‐Lado, N., Ruibal, Á., & Aguiar, P. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101837 · Cited by 74
“These definitions are widely used nowadays in clinical trials of disease-modifying drugs (Cummings et al., 2017).”
BackgroundThe Role of Genetics in Advancing Precision Medicine for Alzheimer’s Disease—A Narrative Review
Freudenberg‐Hua, Y., Li, W., & Davies, P. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00108 · Cited by 80
“Ongoing drug trials include targeting anti-amyloid, anti-tau, anti-inflammatory, neuroprotection, stem cell therapy, and metabolism (136).”
BackgroundAmyloid Cascade Hypothesis for the Treatment of Alzheimer’s Disease: Progress and Challenges
Wu, T., Ding, L., Cheng, Y., Jiang, S., Riaz, M. W., Fu, N., Mou, C., Ye, M., & Zheng, Y. (2022) · Aging and Disease · doi:10.14336/ad.2022.0412 · Cited by 81
“However, the clinical trials of drugs targeting Aβ are challenging with a 99% failure rate [13-15].”
BackgroundHave there been improvements in Alzheimer’s disease drug discovery over the past 5 years?
Cacabelos, R. (2018) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2018.1457645 · Cited by 72
Lo, C. H., Lim, C. K., Ding, Z., Wickramasinghe, S. P., Braun, A. R., Ashe, K. H., Rhoades, E. R., Thomas, D. D., & Sachs, J. N. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.4954 · Cited by 65
Fernández‐Ruíz, J. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14382 · Cited by 70
Farrell, M. E., Papp, K. V., Buckley, R. F., Jacobs, H. I. L., Schultz, A. P., Properzi, M. J., Vannini, P., Hanseeuw, B. J., Rentz, D. M., Johnson, K. A., et al. (2022) · Neurology · doi:10.1212/wnl.0000000000200137 · Cited by 64
de Wilde, A., van Buchem, M. M., Otten, R. H. J., Bouwman, F. H., Stephens, A. W., Barkhof, F., Scheltens, P., & van der Flier, W. M. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0398-3 · Cited by 65
“Nevertheless, amyloid PET is already incorporated in anti-amyloid trials (> 15) as a screening instrument to identify individuals with Alzheimer’s pathology, either cognitively normal (CN) or with MCI, and result disclosure is a necessity of design [24, 25].”
Predictions of Alzheimer’s disease treatment and care costs in European countries
Cimler, R., Marešová, P., Kühnová, J., & Kuča, K. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210958 · Cited by 68
Firth, N. C., Primativo, S., Brotherhood, E., Young, A. L., Yong, K. X. X., Crutch, S. J., Alexander, D. C., & Oxtoby, N. P. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12083 · Cited by 65
“(3) Wider applicationof our newmethod inother neurodegenerativediseases and beyond neuropsychological test scores, including data-driven subtypingof diseases.”
BackgroundTau and atrophy: domain-specific relationships with cognition
Initiative, A. D. N., Digma, L. A., Madsen, J. R., Reas, E. T., Dale, A. M., Brewer, J. B., & Banks, S. J. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0518-8 · Cited by 66
The road to precision medicine: Eliminating the “One Size Fits All” approach in Alzheimer’s disease
Behl, T., Kaur, I., Sehgal, A., Singh, S., Albarrati, A., Albratty, M., Najmi, A., Meraya, A. M., & BUNGAU, S. G. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113337 · Cited by 67
AI-driven fusion of multimodal data for Alzheimer’s disease biomarker assessment
Jasodanand, V. H., Kowshik, S. S., Puducheri, S., Romano, M. F., Xu, L., Au, R., & Kolachalama, V. B. (2025) · Nature Communications · doi:10.1038/s41467-025-62590-4 · Cited by 76
Recent Progress in the Pharmacotherapy of Alzheimer’s Disease
Khoury, R., Patel, K., Gold, J., Hinds, S., & Grossberg, G. T. (2017) · Drugs & Aging · doi:10.1007/s40266-017-0499-x · Cited by 62
N-alkylpiperidine carbamates as potential anti-Alzheimer’s agents
Košak, U., Strašek, N., Knez, D., Jukič, M., Žakelj, S., Zahirović, A., Pišlar, A. H., Brazzolotto, X., Nachon, F., Kos, J., et al. (2020) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2020.112282 · Cited by 61
Challenges and opportunities for improving the landscape for Lewy body dementia clinical trials
Goldman, J. G., Forsberg, L. K., Boeve, B. F., Armstrong, M. J., Irwin, D. J., Ferman, T. J., Galasko, D. R., Galvin, J. E., Kaufer, D., Leverenz, J. B., et al. (2020) · Alzheimer s Research & Therapy · doi:10.1186/s13195-020-00703-5 · Cited by 62
Chen, F., Zhao, Y. Y., & Chen, H. (2018) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2018.3957 · Cited by 60
“Ad is characterized by neurofibrillary tangles, synaptic dysfunction and neurodegeneration; its incidence is increasing rapidly with the aging of the population as an increasing number of individuals approach the key risk period for this age-related disease (26,27).”
Advances on Therapeutic Strategies for Alzheimer’s Disease: From Medicinal Plant to Nanotechnology
Hassan, N. A., Alshamari, A. K., Hassan, A. A., Elharrif, M. G., Alhajri, A. M., Sattam, M., & Khattab, R. R. (2022) · Molecules · doi:10.3390/molecules27154839 · Cited by 64
“Clinical trials are being conducted using a variety of anti-Aβ monoclonal antibodies and other medicines, including nutraceuticals [12,13].”
BackgroundThe Molecular and Neuropathological Consequences of Genetic Risk for Alzheimer's Dementia
Tasaki, S., Gaiteri, C., Mostafavi, S., Jager, P. L. D., & Bennett, D. A. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00699 · Cited by 61
“However, despite gene discoveries from ever-larger sequencing studies, most clinical trials (Cummings et al., 2017) remain focused on the beta-amyloid pathway identified in familial Alzheimer’s disease (AD) in the early 1990’s (Goate et al.”
BackgroundTripathi, A., Choubey, P. K., Sharma, P., Seth, A., Saraf, P., & Shrivastava, S. (2019) · Bioorganic chemistry (Print) · doi:10.1016/j.bioorg.2019.103506 · Cited by 44
Hampel, H., Vergallo, A., Giorgi, F. S., Kim, S. H., Depypere, H., Graziani, M., Saidi, A., Nisticò, R., & Lista, S. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.001 · Cited by 68
Kumar, N. N., Pizzo, M. E., Nehra, G., Wilken-Resman, B., Boroumand, S., & Thorne, R. G. (2018) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.8b00548 · Cited by 59
Alzheimer’s Disease: Combination Therapies and Clinical Trials for Combination Therapy Development
Cummings, J. L., Osse, A. M. L., Kinney, J. W., Cammann, D., & Chen, J. (2024) · CNS Drugs · doi:10.1007/s40263-024-01103-1 · Cited by 63
Self-citationRash, B. G., Ramdas, K. N., Agafonova, N., Naioti, E., McClain‐Moss, L., Zainul, Z., Varnado, B., Peterson, K., Brown, M. T., Leal, T., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-03559-0 · Cited by 71
Big Data and Dementia: Charting the Route Ahead for Research, Ethics, and Policy
Ienca, M., Vayena, E., & Blasimme, A. (2018) · Frontiers in Medicine · doi:10.3389/fmed.2018.00013 · Cited by 65
“According to a study of the drug development pipeline for AD in 2017, current efforts focus mainly on disease-modifying therapies (DMTs) (3), and most of DMT agents in phase III AD trials (as reported on https://clinicaltrials.”
BackgroundPeng, Y., Yuan, M., Xin, J., Liu, X., & Wang, J. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa563 · Cited by 59
Metadata
- Authors
- Cummings, J., Lee, G., Mortsdorf, T., Ritter, A., & Zhong, K.
- Affiliations
- Cleveland Clinic (US)
- Cleveland Clinic Lou Ruvo Center for Brain Health Las Vegas NV USA
- Touro University Nevada Henderson NV USA
- Corresponding author
- Cummings, Jeffrey
- Venue
- Alzheimer's & Dementia: Translational Research & Clinical Interventions
- Publisher
- Wiley
- Published
- 2017-05-24
- Volume
- 3
- Issue
- 3
- Pages
- 367-384
- ISSN
- 2352-8737 (ISSN-L)
- PMC
- PMC5651419
- OpenAlex
- W2617072792
- Cited by
- 549
- References
- 47
- Citations by year
- 2026: 14 · 2025: 53 · 2024: 48 · 2023: 52 · 2022: 67 · 2021: 59 · 2020: 53 · 2019: 91 · 2018: 103 · 2017: 7
- FWCI
- 52.02
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia Translational Research & Clinical Interventions (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Digital Scholarship - UNLV (University of Nevada Reno) (submittedVersion, cc-by-nc)
- Funders
- National Institute on Aging (R01AG084250 R56AG074001 U01AG073323 R01AG066707 R01AG076448 R01AG082118 RF1AG082211 R21AG083003 R35AG71476)
- National Institute of General Medical Sciences (NIA R25AG083721, NIA R35AG71476, P20GM109025)
- National Institute of Neurological Disorders and Stroke (RF1NS133812)
- 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, drug development pipeline, clinical trials, disease-modifying therapy, prodromal Alzheimer's disease, preclinical Alzheimer's disease, amyloid imaging, biomarkers, clinical trial participants
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
