Cited by 556Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

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 access

Cummings, Jeffrey, Lee, Garam, Mortsdorf, Travis, Ritter, Aaron, Zhong, Kate·2017·Alzheimer's & Dementia: Translational Research & Clinical Interventions

DOI 10.1016/j.trci.2017.05.002PMC PMC5651419

Open this paper in CoChat — free account

Abstract

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.

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

Crossref · 10.1016/j.trci.2017.05.002

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Fig. 1 Agents in clinical trials for the treatment of Alzheimer's disease in 2017 (from clinicaltrials.gov accessed 1/5/2017). Abbreviations: ATP, adenosine triphosphate; BNC, bisnorcymserine; GM-CSF, granulocyte-macrophage colony-stimulating factor; OAA, oxaloacetate; IVIG, intravenous immunoglobulin; SLAT, simvastatin + L-arginine + tetrahydrobiopterin.CC BY-NC-ND · PubMed Central

Fig. 2 Mechanisms of action of agents in phase II. Abbreviation: BACE, β-site amyloid precursor protein cleaving enzyme.CC BY-NC-ND · PubMed Central

Fig. 3 Mechanisms of action of agents in phase III. Abbreviation: BACE, β-site amyloid precursor protein cleaving enzyme.CC BY-NC-ND · PubMed Central

Fig. 4 Illustration of drug mechanism (phase III agents) and the proposed biology of Alzheimer's disease. (A) Amyloid cascade. (B) Downstream pathophysiology. Abbreviation: BACE, β-site amyloid precursor protein cleaving enzyme.CC BY-NC-ND · PubMed Central

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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].”
Background
Alzheimer’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-citation
2015 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].”
Background
Clinical 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
Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup
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
DT‐01‐04: The efficacy of RVT‐101, a 5‐ht6 receptor antagonist, as an adjunct to donepezil in adults with mild‐to‐moderate Alzheimer's disease: Completer analysis of a phase 2b study
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
The Alzheimer's Disease Neuroimaging Initiative 3: Continued innovation for clinical trial improvement
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

Show all 47 references

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

Sorted by citations

Items 301–400 of 556

Exploring Potential of Alkaloidal Phytochemicals Targeting Neuroinflammatory Signaling of Alzheimer's Disease
Uddin, M. S., Kabir, M. T., Mamun, A. A., Behl, T., Mansouri, R. A., Aloqbi, A. A., Perveen, A., Hafeez, A., & Ashraf, G. M. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200531151004 · Cited by 16
In vitro Tau Aggregation Inducer Molecules Influence the Effects of MAPT Mutations on Aggregation Dynamics
Ingham, D. J., Hillyer, K. M., McGuire, M. J., & Gamblin, T. C. (2022) · Biochemistry · doi:10.1021/acs.biochem.2c00111 · Cited by 13
A Systematic Review of Antiamyloidogenic and Metal-Chelating Peptoids: Two Structural Motifs for the Treatment of Alzheimer’s Disease
Young, S. C. (2018) · Molecules · doi:10.3390/molecules23020296 · Cited by 14
Setbacks and promises for drugs against Alzheimer's disease
Rinaldi, A. C. (2018) · EMBO Reports · doi:10.15252/embr.201846714 · Cited by 14
“Cummings and colleagues noted that, in many cases, the recruitment period is longer than the treatment period, and failure of meeting the recruitment goal is not rare [8].”
Background
Therapeutic effects of crude extracts of Bacopa floribunda on beta-amyloid 1-42-induced Alzheimer’s disease via suppression of dyslipidemia, systemic inflammation and oxidative stress in male Wistar Rats
Oyeleke, M. B., Oni, H. T., Arokoyo, O. L., & Owoyele, B. V. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e09255 · Cited by 12
Integrated analyses of brain and platelet omics reveal their common altered and driven molecules in Alzheimer's disease
Yu, H., Li, M., Pan, Q., Liu, Y., Zhang, Y., He, T., Yang, H., Xiao, Y., Weng, Y., Gao, Y., et al. (2022) · MedComm · doi:10.1002/mco2.180 · Cited by 11
“1,2 However, the current therapeutic studies by targeting A β plaques and tau have been challenged, 3 suggesting the involvement of complex mechanisms in AD.”
Caregiver Burden and Quality of Life Across Alzheimer’s Disease Severity Stages
Wester, V., Handels, R. L. H., Wolfs, C. A. G., & Kanters, T. A. (2023) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000558 · Cited by 13
Can we predict amyloid deposition by objective cognition and regional cerebral blood flow in patients with subjective cognitive decline?
Funaki, K., Nakajima, S., Noda, Y., Wake, T., Ito, D., Yamagata, B., Yoshizaki, T., Kameyama, M., Nakahara, T., Murakami, K., et al. (2019) · Psychogeriatrics · doi:10.1111/psyg.12397 · Cited by 14
Exploring the zinc-related transcriptional landscape in Alzheimer’s disease
Shippy, D. C., & Ulland, T. K. (2022) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2022.06.002 · Cited by 15
Targeting Alzheimer’s Disease at the Right Time and the Right Place: Validation of a Personalized Approach to Diagnosis and Treatment
Gauthier, S. G., Ng, K. P., Pascoal, T. A., Zhang, H., & Rosa‐Neto, P. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179924 · Cited by 13
“Promising strategies to overcome these difficulties include sharing placebo groups, as currently done in the DIAN-TU RCTs, futility analysis, adaptive designs, patients, and volunteer registries.”
BackgroundInfluential
Dihydroquinoline Carbamate DQS1-02 as a Prodrug of a Potent Acetylcholinesterase Inhibitor for Alzheimer’s Disease Therapy: Multigram-Scale Synthesis, Mechanism Investigations, in Vitro Safety Pharmacology, and Preliminary in Vivo Toxicology Profile
Allix, F., Gembus, V., Coquet, L., Hubert‐Roux, M., Chan, P., Truong, L., Sebban, M., Coadou, G., Oulyadi, H., Papamicaël, C. A., et al. (2018) · ACS Omega · doi:10.1021/acsomega.8b02121 · Cited by 13
Marine bacterial extracts as a new rich source of drugs against Alzheimer’s disease
Zhu, B., Li, Z., Qian, P., & Herrup, K. (2019) · Journal of Neurochemistry · doi:10.1111/jnc.14847 · Cited by 13
“Unfortunately, most have only shown weak therapeutic effects and all of them have failed in advanced clinical trials (Cummings et al. 2017; Cummings et al. 2018).”
Background
Phenotypic Differences between the Alzheimer’s Disease-Related hAPP-J20 Model and HeterozygousZbtb20Knock-Out Mice
Gulbranson, D. R., Ho, K., Yu, G.-Q., Yu, X., Das, M. M., Shao, E., Kim, D., Zhang, W. J., Choudhary, K., Thomas, R., et al. (2021) · eNeuro · doi:10.1523/eneuro.0089-21.2021 · Cited by 14
Trans-Channel Fluorescence Learning Improves High-Content Screening for Alzheimer's Disease Therapeutics
Wong, D. R., Conrad, J. C., Johnson, N. R., Ayers, J. I., Laeremans, A., Lee, J. C., Lee, J., Prusiner, S. B., Bandyopadhyay, S., Butte, A. J., et al. (2021) · Nature Machine Intelligence · doi:10.1038/s42256-022-00490-8 · Cited by 13
Cortical neurodegeneration caused by Psen1 mutations is independent of Aβ
Yan, K., Zhang, C., Kang, J., Montenegro, P., & Shen, J. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2409343121 · Cited by 11
Present and future use of exosomes containing proteins and RNAs in neurodegenerative diseases for synaptic function regulation: A comprehensive review
Liu, Z., Cheng, L., Cao, W., Shen, C., Qiu, Y., Li, C., Xiong, Y., Yang, S., Chen, Z., Yin, X., et al. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.135826 · Cited by 13
Design of Tau Aggregation Inhibitors Using Iterative Machine Learning and a Polymorph-Specific Brain-Seeded Fibril Amplification Assay
Santambrogio, A., Horne, R. I., Metrick, M. A., Gallagher, N. C. T., Brotzakis, Z. F., Rinauro, D. J., Vourkou, E., Papanikolopoulou, K., Skoulakis, E. M. C., Linse, S. S., et al. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.5c12812 · Cited by 12
A phenotypic approach to the discovery of compounds that promote non-amyloidogenic processing of the amyloid precursor protein: Toward a new profile of indirect β-secretase inhibitors
Gay, M., Evrard, C., Descamps, F., Carato, P., Renault, N., Coevoet, M., Eddarkaoui, S., Baud, C., Larchanché, P.-E., Buée, L., et al. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.08.092 · Cited by 14
“Therefore, alternative therapeutic options are urgently needed and over the past few years, much effort has been dedicated to the development of disease-modifying therapeutics [3].”
Background
Alzheimer's Aβ1‐40 peptide degradation by thermolysin: evidence of inhibition by a C‐terminal Aβ product
Leite, J. P., & Gales, L. (2018) · FEBS Letters · doi:10.1002/1873-3468.13285 · Cited by 12
Narrative review: recent advances in doll therapy for Alzheimer’s disease
Cai, X., Zhou, L., Han, P., Deng, X., Zhu, H., Fang, F., & Zhang, Z. (2021) · Annals of Palliative Medicine · doi:10.21037/apm-21-853 · Cited by 12
Exploring the potential of targeting insulin-like growth factor-1 through network pharmacology, molecular docking, molecular dynamics, and experimental validation of antioxidant and anti-inflammatory activities
Prakash, P., Gayathiri, E., Rahaman, M., Periyasami, G., Pandiaraj, S., Pratheep, T., Selvam, K., Chaudhari, S. Y., Thirumalaivasan, N., Thomas, J., et al. (2023) · South African Journal of Botany · doi:10.1016/j.sajb.2023.09.052 · Cited by 12
The Ethyl Acetate Extract of Leaves of Ugni molinae Turcz. Improves Neuropathological Hallmarks of Alzheimer’s Disease in Female APPswe/PS1dE9 Mice Fed with a High Fat Diet
Jara-Moreno, D., Castro-Torres, R. D., Ettcheto, M., Auladell, C., Kogan, M. J., Folch, J., Verdaguer, E., Cano, A. C., Busquets, O., Delporte, C. L., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180174 · Cited by 12
DL0410 ameliorates cognitive deficits in APP/PS1 transgenic mice by promoting synaptic transmission and reducing neuronal loss
Zhou, W., Lian, W., Yan, R., Jia, H., Xu, L., Wang, L., Liu, A., & Du, G. (2019) · Acta Pharmacologica Sinica · doi:10.1038/s41401-019-0312-y · Cited by 12
Improving executive functioning and reducing the risk of Alzheimer's disease with music therapy: A narrative review of potential neural mechanisms
Slade, B., Williams, B. J., Engelbrecht, R., & Ciorciari, J. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251327762 · Cited by 11
Putative pathological mechanisms of late-life depression and Alzheimer’s disease
Hasan, S. M. N., Clarke, C., Strand, T., & Bambico, F. R. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148423 · Cited by 13
Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids
Castro, M. J., Richmond, V., Faraoni, M. B., & Murray, A. P. (2018) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2018.05.012 · Cited by 11
An innovative approach for the treatment of Alzheimer’s disease: the role of peroxisome proliferator-activated receptors and their ligands in development of alternative therapeutic interventions
Piemontese, L. (2018) · Neural Regeneration Research · doi:10.4103/1673-5374.241043 · Cited by 11
“Several of these drugs, such as pioglitazone or insulin itself, are already studied in clinical trials (Cummings et al., 2017) but we cannot yet predict if and when they can be used in AD therapy.”
Human-Derived Brain Models: Windows into Neuropsychiatric Disorders and Drug Therapies
Papariello, A. R., & Litwa, K. (2019) · Assay and Drug Development Technologies · doi:10.1089/adt.2019.922 · Cited by 11
Exploring new avenues for modifying course of progression of Alzheimer's disease: The rise of natural medicine
Lye, S., Aust, C. E., Griffiths, L. R., & Fernandez, F. (2021) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2021.117332 · Cited by 11
Neuroaxonal and cellular damage/protection by prostanoid receptor ligands, fatty acid derivatives and associated enzyme inhibitors
Sharif, N. A. (2022) · Neural Regeneration Research · doi:10.4103/1673-5374.343887 · Cited by 11
“, 2021), seem to have been tested in the AD patients, and no other PGreceptor-related targets appear under investigation (Cummings et al., 2017).”
Background
Past and Future of Drug Treatments for Alzheimer's Disease
Kim, S. Y. (2018) · 신경정신의학 · doi:10.4306/jknpa.2018.57.1.30 · Cited by 11
Photopharmacology in Alzheimer's Disease
Rodríguez‐Soacha, D. A., & Decker, M. W. (2018) · Advanced Therapeutics · doi:10.1002/adtp.201800037 · Cited by 11
Inflammation in Alzheimer’s disease: A friend or foe?
Chiroma, S. M., Baharuldin, M. T. H., Taib, C. N. M., Amom, Z., Jagadeesan, S., & Moklas, M. A. M. (2018) · Biomedical Research and Therapy · doi:10.15419/bmrat.v5i8.464 · Cited by 11
“The other pathological hallmark of AD is the presence of NFTs [10].”
BackgroundInfluential
Effects of BIS-MEP on Reversing Amyloid Plaque Deposition and Spatial Learning and Memory Impairments in a Mouse Model of β-Amyloid Peptide- and Ibotenic Acid-Induced Alzheimer’s Disease
Wang, Y., Xia, J., Shen, M., Zhou, Y., Wu, Z., Shi, Y., Xu, J., Hou, L., Zhang, R., Qiu, Z., et al. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00003 · Cited by 11
“Currently, the main drug development pipelines focus on anti-amyloid, anti-tau, neuroprotective and neurotransmitter-based strategies (Cummings et al., 2017).”
Background
The protective role of miR-132 targeting HMGA2 through the PI3K/AKT pathway in mice with Alzheimer's disease.
Liu, X., Wang, H., Bei, J., Zhao, J., Jiang, G., & Liu, X. (2021) · PubMed Central · Cited by 10
Enalaprilat Inhibits Zinc-Dependent Oligomerization of Metal-Binding Domain of Amyloid-beta Isoforms and Protects Human Neuroblastoma Cells from Toxic Action of these Isoforms
Kozin, S. A., Polshakov, V. I., Mezentsev, Y. V., Ivanov, A. S., Zhokhov, S. S., Yurinskaya, M. M., Винокуров, М. Г., Makarov, A. А., & Mitkevich, V. A. (2018) · Molecular Biology · doi:10.1134/s0026893318040106 · Cited by 11
Nuclear factor‐kappa B: Glucocorticoid‐induced leucine zipper interface analogs suppress pathology in an Alzheimer's disease model
Srinivasan, M., Lahiri, N. K., Thyagarajan, A., Witek, E., Hickman, D. L., & Lahiri, D. K. (2018) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2018.04.004 · Cited by 11
In-Frame and Frameshift Mutations in Zebrafish Presenilin 2 Affect Different Cellular Functions in Young Adult Brains
Barthelson, K., Pederson, S., Newman, M., Jiang, H., & Lardelli, M. T. (2021) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-200279 · Cited by 11
Naturally-Occurring Antibodies Against Bim are Decreased in Alzheimer’s Disease and Attenuate AD-type Pathology in a Mouse Model
Jian, J.-M., Fan, D., Tian, D., Cheng, Y., Sun, P., Tan, C., Zeng, G., He, C.-Y., Wang, Y., Zhu, J., et al. (2022) · Neuroscience Bulletin · doi:10.1007/s12264-022-00869-y · Cited by 11
Feasibility of Using a Novel, Multimodal Motor Function Assessment Platform With Machine Learning to Identify Individuals With Mild Cognitive Impairment
Hall, J. B., Akter, S., Rao, P. R., Kiselica, A. M., Ranum, R. M., Thomas, J. M., & Guess, T. M. (2024) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000646 · Cited by 10
Who funds Alzheimer's disease drug development?
Cummings, J. L., Bauzon, J. S., & Lee, G. (2021) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12185 · Cited by 9
Self-citation
Impact of non‐binding FDA guidances on primary endpoint selection in Alzheimer's disease trials
Yu, J. C., Hlávka, J. P., Joe, E., RICHMOND, F. J. R., & Lakdawalla, D. (2022) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12280 · Cited by 9
In Silico Screening of Natural Compounds for Candidates 5HT6 Receptor Antagonists against Alzheimer’s Disease
Bojić, T., Senćanski, M., Perović, V., Milićević, J. S., & Glišić, S. (2022) · Molecules · doi:10.3390/molecules27092626 · Cited by 10
“The importance of finding new dementia treatments was also recognized by the G7 meeting, where it was stated that new efficient medications need to be developed by 2025 [34,35].”
Background
Memory Loss and the Onset of Alzheimer’s Disease Could Be Under the Control of Extracellular Heat Shock Proteins
Arispe, N. J., & Maio, A. D. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180161 · Cited by 11
“In spite of this intense basic and clinical research progress, no effective cure or prevention has come to light so far [3].”
Using Direct-to-Consumer Genetic Testing Results to Accelerate Alzheimer Disease Clinical Trial Recruitment
Ryan, M. M., Cox, C. G., Witbracht, M. G., Hoang, D. K., Gillen, D. L., & Grill, J. D. (2020) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000421 · Cited by 9
An Overview of β-Amyloid Cleaving Enzyme 1 (BACE1) in Alzheimer's Disease Therapy: Elucidating its Exosite-Binding Antibody and Allosteric Inhibitor
Ugbaja, S. C., Lawal, M. M., & Kumalo, H. M. (2021) · Current Medicinal Chemistry · doi:10.2174/0929867328666210608145357 · Cited by 11
Reconsidering the overdiagnosis of mild cognitive impairment for dementia prevention among adults aged ≥80 years
Maki, Y. (2021) · Journal of Primary Health Care · doi:10.1071/hc20115 · Cited by 11
Characterizing the Chemical Space of γ-Secretase Inhibitors and Modulators
Santiago, Á., Guzmán‐Ocampo, D. C., Aguayo‐Ortiz, R., & Domı́nguez, L. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00313 · Cited by 10
Aniba canelilla (Kunth) Mez essential oil and its primary constituent, 1-nitro-2-phenylethane, inhibits acetylcholinesterase and reverse memory impairment in rodents
de Campos, D. L., Queiroz, L. Y., Fontes-Júnior, E. A., Pinheiro, B. G., da Silva, J. K. R., Maia, C. D. S. F., & Maia, J. G. S. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.116036 · Cited by 9
Speech-based digital cognitive assessments for detection of mild cognitive impairment: Validation against paper-based neurocognitive assessment scores
Alexopoulou, Z.-S., Köhler, S., Mallick, E., Tröger, J., Linz, N., Spruth, E. J., Fließbach, K., Bartels, C., Rostamzadeh, A., Glanz, W., et al. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251343296 · Cited by 9
Comparison of the diagnostic accuracy of five cross-cultural cognitive screening instruments for dementia and mild cognitive impairment in a multicultural memory clinic sample
Nielsen, T. R., Jørgensen, K., Delgado‐Álvarez, A., Franzen, S., Lozano-Ruiz, Á., Özden, M., Palisson, J., Mukadam, N., & Waldemar, G. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251351037 · Cited by 10
Network analysis-guided drug repurposing strategies targeting LPAR receptor in the interplay of COVID, Alzheimer’s, and diabetes
Malar, D. S., Verma, K., Prasanth, M. I., Tencomnao, T., & Brimson, J. M. (2024) · Scientific Reports · doi:10.1038/s41598-024-55013-9 · Cited by 9
Dementias Platform UK Clinical Studies and Great Minds Register: protocol of a targeted brain health studies recontact database
Koychev, I. G., Young, S., Holve, H., Yehuda, M. B., & Gallacher, J. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-040766 · Cited by 9
Exercise engagement drives changes in cognition and cardiorespiratory fitness after 8 weeks of aerobic training in sedentary aging adults at risk of cognitive decline
Hinchman, C. A., Cabral, D. F., Ciesla, M. R., Flothmann, M., Nunez, C., Rice, J., Loewenstein, D., Kitaigorodsky, M., Cahalin, L. P., Rundek, T., et al. (2022) · Frontiers in Rehabilitation Sciences · doi:10.3389/fresc.2022.923141 · Cited by 10
Lecanamab Ushers in a New Era of Anti‐Amyloid Therapy for Alzheimer's Disease
Musiek, E. S., McDade, E., & Holtzman, D. M. (2023) · Annals of Neurology · doi:10.1002/ana.26643 · Cited by 9
Translational Scoring of Candidate Treatments for Alzheimer’s Disease: A Systematic Approach
Cummings, J. L. (2020) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000507569 · Cited by 9
Self-citation
Alzheimer’s Disease and Dementia
Lewis, P. A., & Spillane, J. E. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-811069-0.00002-1 · Cited by 9
Loss of estrogen unleashing neuro-inflammation increases the risk of Alzheimer’s disease in womenPreprint
Li, F., Oh, I. Y., Kumar, S., Eteleeb, A. M., Gupta, A., Buchser, W., Xiong, C., Cole, S. F., McDade, E., Karch, C. M. M., et al. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.19.508592 · Cited by 9
Neuroprotective effects of a combination of Boswellia papyrifera and Syzygium aromaticum on AlCl3 induced Alzheimer's disease in male albino rat
Aljàrari, R. M. (2023) · Brazilian Journal of Biology · doi:10.1590/1519-6984.272466 · Cited by 8
State-of-the-art surfactant-based coatings for biomaterials: Innovations, applications, and future prospects in biomedical engineering
Nagaraj, K. (2025) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2025.125879 · Cited by 8
From Alzheimer’s Disease to Anxiety, Epilepsy to Schizophrenia: A Comprehensive Dive Into Neuro-Psychiatric Disorders
Grezenko, H., Rodoshi, Z. N., Mimms, C. S., Ahmed, M., Sabani, A., Hlaing, M. S., Batu, B. J., Hundesa, M. I., Ayalew, B. D., Shehryar, A., et al. (2024) · Cureus · doi:10.7759/cureus.58776 · Cited by 10
Interpreting cognitive decline in the face of cognitive reserve
Bialystok, E., Anderson, J. A. E., & Grundy, J. G. (2018) · Linguistic Approaches to Bilingualism · doi:10.1075/lab.18040.bia · Cited by 9
Implementing a Memory Clinic Model to Facilitate Recruitment into Early Phase Clinical Trials for Mild Cognitive Impairment and Alzheimer's Disease
Park, L., Kouhanim, C., Lee, S., Mendoza, Z., Patrick, K. E., Gertsik, L., Aguilar, C., Gullaba, D., Semenova, S., & Jhee, S. S. (2019) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2019.8 · Cited by 8
Effect of memantine on expression of Bace1-as and Bace1 genes in STZ-induced Alzheimeric rats
Azadfar, P., Noormohammadi, Z., Noroozıan, M., Eidi, A., & Mortazavi, P. (2020) · Molecular Biology Reports · doi:10.1007/s11033-020-05629-7 · Cited by 8
Efficacy of preclinical pharmacological interventions against alterations of neuronal network oscillations in Alzheimer's disease: A systematic review
Isla, A. G., Balleza‐Tapia, H., & Fisahn, A. (2021) · Experimental Neurology · doi:10.1016/j.expneurol.2021.113743 · Cited by 9
“Great efforts have been made to discover an effective pharmacological strategy to counteract memory impairment in AD (Cummings et al., 2020; Cummings et al., 2019; Cummings et al., 2018; Cummings et al., 2017; Cummings et al., 2016).”
Background
Gene Therapy in Alzheimer Disease—It May Be Feasible, but Will It Be Beneficial?
Honig, L. S. (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2017.4029 · Cited by 8
DeepDrug: An Expert-led Domain-specific AI-Driven Drug-Repurposing Mechanism for Selecting the Lead Combination of Drugs for Alzheimer’s Disease
Li, V. O., Han, Y., Kaistha, T., Zhang, Q., Downey, J., Gozes, I., & Lam, J. C. (2024) · doi:10.1101/2024.07.06.24309990 · Cited by 8
Targeting calciumopathy for neuroprotection: focus on calcium channels Cav1, Orai1 and P2X7
Torres-Rico, M., García-Calvo, V., Gironda-Martínez, A., Pascual-Guerra, J., Garcı́a, A. G., & Maneu, V. (2024) · Cell Calcium · doi:10.1016/j.ceca.2024.102928 · Cited by 8
“So, in 2017 over 100 drugs were undergoing CTs in AD patients [285,286].”
Background
Efficacy of acupuncture in patients with mild Alzheimer’s disease and its impact on gut microbiota: Study protocol for a randomized sham-controlled trial
Kong, X., Ma, Z., Tang, R., Wang, X., Wei, K., Yang, G., Yang, Y., Zhao, Y., Zhang, D., Xie, C., et al. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1014113 · Cited by 8
Dysregulated AEBP1 and COLEC12 Genes in Late-Onset Alzheimer’s Disease: Insights from Brain Cortex and Peripheral Blood Analysis
Asadie, M., Miri, A., Badri, T., Nejad, J. H., & Gharechahi, J. (2024) · Journal of Molecular Neuroscience · doi:10.1007/s12031-024-02212-8 · Cited by 7
“According to a recent assessment, there are roughly 28 medications in the third clinical trial phase, 74 in the second trial phase, and 30 in the first clinical trial phase; however, the failure rate is significantly high owing to inadequate proof of effectiveness (Cummings et al. 2017, 2019).”
The economic case for scaling up health research and development: Lessons from the COVID-19 pandemic
Tortorice, D. L., Rappuoli, R., & Bloom, D. E. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2321978121 · Cited by 7
The Function of Selenium in Central Nervous System: Lessons from MsrB1 Knockout Mouse Models
Shi, T., Song, J., You, G., Yang, Y., Liu, Q., & Li, N. (2021) · Molecules · doi:10.3390/molecules26051372 · Cited by 7
“The drugs that inhibit the production and aggregation of Aβ failed to achieve clinical success in curing AD [71,72].”
Background
Progressive Motor and Non-Motor Symptoms in Park7 Knockout Zebrafish
Chavali, L., Yddal, I., Bifulco, E., Mannsåker, S., Røise, D., Law, J. O., Frøyset, A. K., Grellscheid, S. N., & Fladmark, K. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076456 · Cited by 7
“Weight loss is among the non-motor symptoms associated to parkinsonism, and early weight loss predicts a poor outcome [24,25].”
Background
Is it time to rethink the Alzheimer's disease drug development strategy by targeting its silent phase?
Braudeau, J., Souchet, B., Audrain, M., Billoir, B., Lecanu, L., & Tada, S. (2018) · Neural Regeneration Research · doi:10.4103/1673-5374.226389 · Cited by 8
Sleep modulating agents
Choi, Y., & Raymer, B. K. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.06.043 · Cited by 7
Fecal Microbiota Transplantation Decreases Amyloid Load and Improves Cognition in Alzheimer’sPreprint
Elangovan, S., Borody, T. J., & Holsinger, R. M. D. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/687376 · Cited by 7
Combined Metabolic Activators Improves Cognitive Functions in Alzheimer's DiseasePreprint
Yuluğ, B., Altay, Ö., Li, X., Hanoğlu, L., Çankaya, Ş., Lam, S. C. C., Yang, H., Coşkun, E., İdil, E., Nogaylar, R., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3924201 · Cited by 7
Weakly activated core inflammation pathways were identified as a central signaling mechanism contributing to the chronic neurodegeneration in Alzheimer’s diseasePreprint
Li, F., Eteleeb, A. M., Buchser, W., Wang, G., Xiong, C., Payne, P., McDade, E., Karch, C. M. M., Harari, O., & Cruchaga, C. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.08.30.458295 · Cited by 7
Path-based reasoning for biomedical knowledge graphs with BioPathNetPreprint
Hu, Y., Oleshko, S., Firmani, S., Zhu, Z., Cheng, H., Wörheide, M. A., Arnold, M., Colomé‐Tatché, M., Tang, J., Xhonneux, S., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.17.599219 · Cited by 7
Comparison between dynamic versus static models and real-time monitoring of neuronal dysfunction in an amyloid-β induced neuronal toxic model on a chip platform
Liang, C.-C., Chen, P., Liu, N., & Lee, I. (2024) · Lab on a Chip · doi:10.1039/d3lc00507k · Cited by 6
Using dynamic microsimulation to project cognitive function in the elderly population
Wei, Y., Heun‐Johnson, H., & Tysinger, B. (2022) · PLoS ONE · doi:10.1371/journal.pone.0274417 · Cited by 6
Isobavachalcone ameliorates Alzheimer disease pathology by autophagy-mediated clearance of amyloid beta and inhibition of NLRP3 inflammasome in primary astrocytes and 5x-FAD mice
Kour, D., Khajuria, P., Sharma, K., Sharma, A., Sharma, A., Ali, S. M., Wazir, P., Ramajayan, P., Sawant, S. D., Nandi, U., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1525364 · Cited by 8
An Acquaintance with An Aging Society
Yamada, K. (2019) · Social Sciences · doi:10.3390/socsci8040110 · Cited by 7
Analyses of natural courses of Japanese patients with Alzheimer's disease using placebo data from placebo‐controlled, randomized clinical trials: Japanese Study on the Estimation of Clinical course of Alzheimer's disease
Watanabe, M., Nakamura, Y., Yoshiyama, Y., Kagimura, T., Kawaguchi, H., Matsuzawa, H., Tachibana, Y., Nishimura, K., Kubota, N., Kobayashi, M., et al. (2019) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.07.004 · Cited by 6
“Success rate of development of drugs for AD has been reported to be low, with the lack of understanding of the natural progression of AD being one reason [4], and detailed analyses on the natural courses of AD may also lead to help determine procedures for future clinical studies for AD such as designs of clinical stu…”
Background
Molecular modeling of cardanol-derived AChE inhibitors
Silva, M. D. A., Sette, C. D. B., Kiametis, A. S., Romeiro, L. A. S., & Gargano, R. (2019) · Chemical Physics Letters · doi:10.1016/j.cplett.2019.07.019 · Cited by 6
Modulating innate immune activation states impacts the efficacy of specific Aβ immunotherapy
Levites, Y., Funk, C. C., Wang, X., Chakrabarty, P., McFarland, K. N., Bramblett, B., O’Neal, V., Liu, X., Ladd, T. B., Robinson, M., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00453-4 · Cited by 6
Эналаприлат ингибирует цинкзависимую олигомеризацию металлсвязывающего домена изоформ бета-амилоида и защищает клетки нейробластомы человека от их токсического действия
Kozin, S. A., Polshakov, V. I., Mezentsev, Y. V., Ivanov, A. S., Жохов, С. С., Юринская, М. М., Винокуров, М. Г., Makarov, A. А., & Mitkevich, V. A. (2018) · Molecular Biology · doi:10.1134/s0026898418040109 · Cited by 6
The TAU isoform 1N4R restores vulnerability of MAPT knockout human iPSC-derived neurons to Amyloid beta-induced neuronal dysfunctionPreprint
Buchholz, S., Bell, M. J., Kabbani, M. A. A., Kluge, L., Cagkmak, C., Klimek, J., & Zempel, H. (2022) · Research Square · doi:10.21203/rs.3.rs-2277268/v1 · Cited by 6
Self-Supervised Contrastive Learning to Predict Alzheimer’s Disease Progression with 3D Amyloid-PETPreprint
Kwak, M. G., Su, Y., Chen, K., Weidman, D. A., Wu, T., Lure, F. Y. M., & Li, J. (2023) · medRxiv · doi:10.1101/2023.04.20.23288886 · Cited by 6
Validation of a functional human AD model with four AD therapeutics utilizing patterned ipsc-derived cortical neurons integrated with microelectrode arrays
Caneus, J., Autar, K., Akanda, N., Grillo, M., Long, C. J., Jackson, M., Lindquist, S., Guo, X., Morgan, D., & Hickman, J. J. (2024) · Scientific Reports · doi:10.1038/s41598-024-73869-9 · Cited by 6
Curcumin's multi-target mechanisms in the treatment of Alzheimer's disease and creative modification techniques
Meng, X., Gong, Y., Xiao, F., Cao, Z., Zhuang, Z., Yi, X., Wang, J., Feng, R., Gong, C., & Ni, P. (2025) · Journal of Alzheimer s Disease · doi:10.1177/13872877251344188 · Cited by 6
Replacement of a single residue in an antibody abolishes cognate antigen binding, as predicted by theoretical methods
Scherlo, M., Höveler, A., Mann, M., Gerwert, G., Güldenhaupt, J., Gerwert, K. B., Rudack, T., & Kötting, C. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.10.018 · Cited by 5
APOE ɛ4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer’s Disease
Cardoso, R., Lemos, C., Oliveiros, B., Almeida, M. R., Baldeiras, I., Pereira, C., SANTOS, A. C. D. S., Duro, D., Vieira, D., Santana, I. J., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200556 · Cited by 6
“When considering MCI as a prodromal state of AD (MCI due to AD) [3], it is of major importance to study the risk factors that predict which MCI patients will convert to AD, namely risk genes, as this group of patients represents a target for future disease modifying therapies [4].”
Unveiling the potential of novel indol-3-yl-phenyl allylidene hydrazine carboximidamide derivatives as AChE/BACE 1 dual inhibitors: a combined in silico , synthesis and in vitro study
Sharma, A., Rudrawar, S., Sharma, A., Bharate, S. B., & Jadhav, H. R. (2024) · RSC Advances · doi:10.1039/d4ra04315d · Cited by 5
Associations between antidiabetic medications and cerebrospinal fluid biomarkers of Alzheimer's disease
García‐Lluch, G., Marseglia, A., Royo, L. M., Pardo, J., García-Zamora, M., Baquero, M., Peña‐Bautista, C., Álvarez, L., Westman, E., & Cháfer‐Pericás, C. (2024) · Journal of Alzheimer s Disease · doi:10.1177/13872877241304995 · Cited by 5
Development and Validation of a Rapid and Specific UHPLC–MS/MS Method for Simultaneous Determination of 21 Bioactive Components in Tiantai No. 1 Pill and Rat Plasma
Liang, S., Zeng, Y., Wu, J., Li, Z., Luo, H., & Wu, Z. (2018) · Chromatographia · doi:10.1007/s10337-018-3470-z · Cited by 5
The Amyloid Precursor Protein: More than Just Amyloid- Beta
Jevtic, S. D., & Provias, J. (2019) · Journal of Neurology and Experimental Neuroscience · doi:10.17756/jnen.2019-045 · Cited by 5
“Furthermore, over one hundred AD-targeted clinical trials have been initiated, but to date have failed to yield disease modifying therapy [8, 9].”
Background
Effects of Gentiana delavayi Flower Extract on APP Processing in APP/PS1 CHO Cells
Yang, M., Zhou, K., Li, F., Yang, H., Yin, M., Zhang, L.-H., & Wang, F. (2020) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b19-00720 · Cited by 5
“Ready for What?”: Timing and Speculation in Alzheimer’s Disease Drug Development
Brenman, N. F., & Milne, R. (2021) · Science Technology & Human Values · doi:10.1177/01622439211007196 · Cited by 5
“These companies were involved to differing extents in the development of the project and, indeed, in Alzheimer’s drug development overall (Cummings et al. 2017).”
Background
The Outcomes of Small-Molecule Kinase Inhibitors and the Role of ROCK2 as a Molecular Target for the Treatment of Alzheimer's Disease
Tolomeu, H. V., & Fraga, C. A. M. (2021) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527320666210820092220 · Cited by 5

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
ORCID: Cummings, Jeffrey
Zhong, Kate
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)
DOI: 10.1016/j.trci.2017.05.002
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: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
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

Alzheimer's disease drug development pipeline: 2017

Abstract

Overview

Integrity signals

Figures

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks