Drug repositioning and repurposing for Alzheimer disease
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Drug repositioning and repurposing can enhance traditional drug development efforts and could accelerate the identification of new treatments for individuals with Alzheimer disease (AD) dementia and mild cognitive impairment. Transcriptional profiling offers a new and highly efficient approach to the identification of novel candidates for repositioning and repurposing. In the future, novel AD transcriptional signatures from cells isolated at early stages of disease, or from human neurons or microglia that carry mutations that increase the risk of AD, might be used as probes to identify additional candidate drugs. Phase II trials assessing repurposed agents must consider the best target population for a specific candidate therapy as well as the mechanism of action of the treatment. In this Review, we highlight promising compounds to prioritize for clinical trials in individuals with AD, and discuss the value of Delphi consensus methodology and evidence-based reviews to inform this prioritization process. We also describe emerging work, focusing on the potential value of transcript signatures as a cost-effective approach to the identification of novel candidates for repositioning.
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Repurposed drugs are noted for their extensive safety and tolerance profiles, as well as their potential for multiple uses.
“These drugs are noted for their extensive safety and tolerance profiles, as well as their potential for multiple uses.428,430”
From Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies. (2024) · cites this paper as [430]
Drug repurposing can accelerate the identification of new therapeutic agents for AD.
“Drug repurposing can accelerate the identification of new therapeutic agents for AD [80].”
From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [80]
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McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
Dementia prevention, intervention, and care
Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S. G., Huntley, J., Ames, D., Ballard, C., Banerjee, S., Burns, A., Cohen-Mansfield, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31363-6 · Cited by 6,072 · see citing works
Self-citationLamb, J., Crawford, E. D., Peck, D., Modell, J. W., Blat, I. C., Wrobel, M. J., Lerner, J., Brunet, J.-P., Subramanian, A., Ross, K. N., et al. (2006) · Science · doi:10.1126/science.1132939 · Cited by 5,257 · see citing works
Jack, C. R., Knopman, D. S., Jagust, W. J., Petersen, R. C., Weiner, M. W., Aisen, P. S., Shaw, L. M., Vemuri, P., Wiste, H. J., Weigand, S. D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70291-0 · Cited by 4,396 · see citing works
α-Synuclein Locus Triplication Causes Parkinson's Disease
Singleton, A. B., Farrer, M., Johnson, J., Singleton, A., Hague, S., Kachergus, J., Hulihan, M., Peuralinna, T., Dutra, A., Nussbaum, R., et al. (2003) · Science · doi:10.1126/science.1090278 · Cited by 4,383 · see citing works
A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles
Subramanian, A., Narayan, R., Corsello, S. M., Peck, D. D., Natoli, T. E., Lu, X., Gould, J., Davis, J. F., Tubelli, A. A., Asiedu, J. K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.10.049 · Cited by 3,515 · see citing works
Cholinesterase inhibitors for Alzheimer's disease
Birks, J. S. (2006) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd005593 · Cited by 1,906 · see citing works
β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression
Rothstein, J. D., Patel, S., Regan, M. R., Haenggeli, C., Huang, Y. H., Bergles, D. E., Jin, L., Dykes Hoberg, M., Vidensky, S., Chung, D. S., et al. (2005) · Nature · doi:10.1038/nature03180 · Cited by 1,518 · see citing works
Selective loss of glial glutamate transporter GLT‐1 in amyotrophic lateral sclerosis
Rothstein, J. D., Van Kammen, M., Levey, A. I., Martin, L. J., & Kuncl, R. W. (1995) · Annals of Neurology · doi:10.1002/ana.410380114 · Cited by 1,471 · see citing works
The Study on Cognition and Prognosis in the Elderly (SCOPE)
Lithell, H., Hansson, L., Skoog, I. G., Elmfeldt, D., Albert Hofman, D., Olofsson, B., Trenkwalder, P., & Zanchetti, A. (2003) · Journal of Hypertension · doi:10.1097/00004872-200305000-00011 · Cited by 1,413 · see citing works
Williamson (2019) · doi:10.1001/jama.2018.21442 · Cited by 1,246 · see citing works
Donepezil for dementia due to Alzheimer’s disease.
Birks, J. S., & Harvey, R. J. (2018) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd001190.pub3 · Cited by 1,200 · see citing works
Trial of Solanezumab for Mild Dementia Due to Alzheimer’s Disease
Honig, L. S., Vellas, B., Woodward, M., Boada, M., Bullock, R., Borrie, M., Hager, K., Andreasen, N., Scarpini, E., Liu-Seifert, H., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1705971 · Cited by 1,049 · see citing works
Petersen, R. C. (2016) · CONTINUUM Lifelong Learning in Neurology · doi:10.1212/con.0000000000000313 · Cited by 925 · see citing works
McClean, P. L., Parthsarathy, V., Faivre, E., & Hölscher, C. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0529-11.2011 · Cited by 698 · see citing works
Herpes simplex virus type 1 in brain and risk of Alzheimer's disease
Itzhaki, R. F., Lin, W., Shang, D., Wilcock, G. K., Faragher, B. E., & Jamieson, G. A. (1997) · The Lancet · doi:10.1016/s0140-6736(96)10149-5 · Cited by 671 · see citing works
Randomized trial of verubecestat for prodromal Alzheimer's disease
Egan, M. F., Kost, J., Voss, T., Mukai, Y., Aisen, P. S., Cummings, J. L., Tariot, P. N., Vellas, B., van Dyck, C. H., Boada, M., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812840 · Cited by 545 · see citing works
Self-citationInconsistencies and Controversies Surrounding the Amyloid Hypothesis of Alzheimer's Disease
Morris, G. P., Clark, I. A., & Vissel, B. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0135-5 · Cited by 522 · see citing works
Interactions of Glucagon-Like Peptide-1 (GLP-1) with the Blood-Brain Barrier
Kastin, A. J., Akerstrom, V., & Pan, W. (2002) · Journal of Molecular Neuroscience · doi:10.1385/jmn:18:1-2:07 · Cited by 480 · see citing works
(U.S.), N. L. O. M. (2008) · Journal of Pain & Palliative Care Pharmacotherapy · doi:10.1080/15360280801989377 · Cited by 474 · see citing works
Herpes simplex virus type 1 DNA is located within Alzheimer's disease amyloid plaques
Wozniak, M., Mee, A., & Itzhaki, R. (2009) · The Journal of Pathology · doi:10.1002/path.2449 · Cited by 464 · see citing works
β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease
Mittal, S., Bjørnevik, K., Im, D. S., Flierl, A., Dong, X., Locascio, J. J., Abo, K. M., Long, E., Jin, M., Xu, B. Y., et al. (2017) · Science · doi:10.1126/science.aaf3934 · Cited by 417 · see citing works
Tzeng, N.-S., Chung, C.-H., Lin, F.-H., Chiang, C.-P., Yeh, C.-B., Huang, S.-Y., Lu, R.-B., Chang, H.-A., Kao, Y.-C., Yeh, H.-W., et al. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0611-x · Cited by 356 · see citing works
Perry, T., Lahiri, D. K., Sambamurti, K., Chen, D., Mattson, M. P., Egan, J. M., & Greig, N. H. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10611 · Cited by 347 · see citing works
Herpes simplex virus infection causes cellular β-amyloid accumulation and secretase upregulation
Wozniak, M. A., Itzhaki, R. F., Shipley, S. J., & Dobson, C. B. (2007) · Neuroscience Letters · doi:10.1016/j.neulet.2007.09.077 · Cited by 339 · see citing works
Latent herpes simplex virus type 1 in normal and Alzheimer's disease brains
Jamieson, G. A., Maitland, N. J., Wilcock, G. K., Craske, J., & Itzhaki, R. F. (1991) · Journal of Medical Virology · doi:10.1002/jmv.1890330403 · Cited by 333 · see citing works
Wang, J., Ho, L., Chen, L., Zhao, Z., Zhao, W., Qian, X., Humala, N., Seror, I., Bartholomew, S. R., Rosendorff, C., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31547 · Cited by 331 · see citing works
Insulin metabolism and the risk of Alzheimer disease: The Rotterdam Study
Schrijvers, E. M. C., Witteman, J. C. M., Sijbrands, E. J. G., Hofman, A., Koudstaal, P. J., & Breteler, M. M. B. (2010) · Neurology · doi:10.1212/wnl.0b013e3181ffe4f6 · Cited by 328 · see citing works
Drug repositioning and repurposing: terminology and definitions in literature
Langedijk, J., Mantel-Teeuwisse, A. K., Slijkerman, D. S., & Schutjens, M.-H. D. B. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.05.001 · Cited by 327 · see citing works
Glutamate Transporters in Neurologic Disease
Maragakis, N. J., & Rothstein, J. D. (2001) · Archives of Neurology · doi:10.1001/archneur.58.3.365 · Cited by 324 · see citing works
Perry, T., Lahiri, D., Chen, D., Zhou, J., Shaw, K., Egan, J., & Greig, N. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.300.3.958 · Cited by 306 · see citing works
Drug repositioning for Alzheimer's disease
Corbett, A., Pickett, J., Burns, A. S., Corcoran, J. P. T., Dunnett, S. B., Edison, P., Hagan, J. J., Holmes, C., Jones, E., Katona, C., et al. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3869 · Cited by 302 · see citing works
Self-citationCukierman-Yaffe, T., Gerstein, H. C., Colhoun, H. M., Diaz, R., García-Pérez, L.-E., Lakshmanan, M., Bethel, A., Xavier, D., Probstfield, J., Riddle, M. C., et al. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30173-3 · Cited by 300 · see citing works
Cudkowicz, M., Titus, S., Kearney, M., Yu, H., Sherman, A., Schoenfeld, D., Hayden, D., Shui, A. M., Brooks, B. R., CONWIT, R. A., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70222-4 · Cited by 243 · see citing works
Brain renin-angiotensin—A new look at an old system
Wright, J. W., & Harding, J. W. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.07.001 · Cited by 233 · see citing works
Hubsher, G., Haider, M., & Okun, M. S. (2012) · Neurology · doi:10.1212/wnl.0b013e31824e8f0d · Cited by 229 · see citing works
Clusterin regulates β-amyloid toxicity via Dickkopf-1-driven induction of the wnt–PCP–JNK pathway
Killick, R., Ribe, E. M., Al-Shawi, R., Malik, B., Hooper, C., Fernandes, C., Dobson, R., Nolan, P. M., Lourdusamy, A., Furney, S., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2012.163 · Cited by 222 · see citing works
Alzheimer’s disease-specific tau phosphorylation is induced by herpes simplex virus type 1
Wozniak, M. A., Frost, A. L., & Itzhaki, R. F. (2009) · Journal of Alzheimer's Disease · doi:10.3233/jad-2009-0963 · Cited by 216 · see citing works
Anderson, C., Teo, K., Gao, P., Arima, H., Dans, A., Unger, T., Commerford, P., Dyal, L., Schumacher, H., Pogue, J., et al. (2011) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70250-7 · Cited by 216 · see citing works
Current advances in using neurotrophic factors to treat neurodegenerative disorders
Weissmiller, A. M., & Wu, C. (2012) · Translational Neurodegeneration · doi:10.1186/2047-9158-1-14 · Cited by 211 · see citing works
Hamilton, A., Patterson, S., Porter, D., Gault, V. A., & Holscher, C. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22565 · Cited by 210 · see citing works
van Gool, W. A., Weinstein, H. C., Scheltens, P., & Walstra, G. J. M. (2001) · The Lancet · doi:10.1016/s0140-6736(01)05623-9 · Cited by 210 · see citing works
Efficacy and Safety of Fasudil in Patients With Stable Angina
Vicari, R. M., CHAITMAN, B. R., Keefe, D. L., Smith, W. B., Chrysant, S. G., Tonkon, M. J., Bittar, N., Weiss, R., Morales-Ballejo, H., & Thadani, U. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.07.047 · Cited by 199 · see citing works
Howard, R., Zubko, O., Bradley, R., Harper, E., Pank, L., O’Brien, J., Fox, C., Tabet, N., Livingston, G., Bentham, P., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2019.3762 · Cited by 194 · see citing works
Self-citationNilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial
Lawlor, B., Segurado, R., Kennelly, S., Olde Rikkert, M. G. M., Howard, R., Pasquier, F., Börjesson-Hanson, A., Tsolaki, M., Lucca, U., Molloy, D. W., et al. (2018) · PLOS Medicine · doi:10.1371/journal.pmed.1002660 · Cited by 193 · see citing works
Hansen, H. H., Fabricius, K., Barkholt, P., Niehoff, M. L., Morley, J. E., Jelsing, J., Pyke, C., Knudsen, L. B., Farr, S. A., & Vrang, N. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-143090 · Cited by 189 · see citing works
Angiotensins in Alzheimer's disease - friend or foe?
Kehoe, P., Miners, S., & Love, S. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.07.006 · Cited by 180 · see citing works
Determining the minimum clinically important differences for outcomes in the DOMINO trial
Howard, R., Phillips, P., Johnson, T., O'Brien, J. T., Sheehan, B., Lindesay, J., Bentham, P., Burns, A., Ballard, C., Holmes, C., et al. (2011) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.2607 · Cited by 179 · see citing works
Self-citationWozniak, M. A., Frost, A. L., Preston, C. M., & Itzhaki, R. F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025152 · Cited by 173 · see citing works
Blood-Brain Glucose Transfer in Alzheimer’s disease: Effect of GLP-1 Analog Treatment
Gejl, M., Brock, B., Egefjord, L., Vang, K., Rungby, J., & Gjedde, A. (2017) · Scientific Reports · doi:10.1038/s41598-017-17718-y · Cited by 163 · see citing works
Val(8)GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice
Gengler, S., McClean, P. L., McCurtin, R. E., Gault, V. A., & Hölscher, C. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.02.014 · Cited by 160 · see citing works
A Pilot Study of Exenatide Actions in Alzheimer’s Disease
Mullins, R. J., Mustapić, M., Chia, C. W., Carlson, O. D., Gulyani, S., Tran, J., Li, Y., Mattson, M. P., Resnick, S. M., Egan, J. M., et al. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190913155950 · Cited by 160 · see citing works
Protective Effects of Intranasal Losartan in the APP/PS1 Transgenic Mouse Model of Alzheimer Disease
Danielyan, L., Klein, R., Hanson, L. R., Buadze, M., Schwab, M. G., Gleiter, C. H., & Frey, W. H. (2010) · Rejuvenation Research · doi:10.1089/rej.2009.0944 · Cited by 158 · see citing works
Fukumoto, Y., Yamada, N., Matsubara, H., Mizoguchi, M., Uchino, K., Yao, A., Kihara, Y., Kawano, M., Watanabe, H., Takeda, Y., et al. (2013) · Circulation Journal · doi:10.1253/circj.cj-13-0443 · Cited by 151 · see citing works
Herpes Zoster and Dementia: A Nationwide Population-Based Cohort Study
Chen, V. C.-H., Wu, S.-I., Huang, K.-Y., Yang, Y.-H., Kuo, T.-Y., Liang, H.-Y., Huang, K.-L., & Gossop, M. (2018) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.16m11312 · Cited by 142 · see citing works
HSV-1 promotes Ca2+-mediated APP phosphorylation and Aβ accumulation in rat cortical neurons
Piacentini, R., Civitelli, L., Ripoli, C., Marcocci, M. E., Chiara, G. D., Garaci, E., Azzena, G. B., Palamara, A. T., & Grassi, C. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.06.009 · Cited by 141 · see citing works
Current and emerging avenues for Alzheimer's disease drug targets
Loera‐Valencia, R., Cedazo-Mı́nguez, Á., Kenigsberg, P.-A., Page, G., Duarte, A. I., Giusti, P., Zusso, M., Robert, P. H., Frisoni, G. B., Cattaneo, A., et al. (2019) · Journal of Internal Medicine · doi:10.1111/joim.12959 · Cited by 139 · see citing works
Ohmachi, S., Watanabe, Y., Mikami, T., Kusu, N., Ibi, T., Akaike, A., & Itoh, N. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3675 · Cited by 139 · see citing works
Ongali, B., Nicolakakis, N., Tong, X., Aboulkassim, T., Papadopoulos, P., Rosa‐Neto, P., Lecrux, C., Imboden, H., & Hamel, É. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.04.018 · Cited by 135 · see citing works
Telmisartan prevented cognitive decline partly due to PPAR-γ activation
Mogi, M., Li, J., Tsukuda, K., Iwanami, J., Min, L., Sakata, A., Fujita, T., Iwai, M., & Horiuchi, M. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2008.08.032 · Cited by 134 · see citing works
Lahiri, D. K., Chen, D., Maloney, B., Holloway, H. W., Yu, Q.-S., Utsuki, T., Giordano, T., Sambamurti, K., & Greig, N. H. (2006) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.112102 · Cited by 134 · see citing works
Effect of phenserine treatment on brain functional activity and amyloid in Alzheimer's disease
Kadir, A., Andreasen, N., Almkvist, O., Wall, A. E., Forsberg, A., Engler, H., Hagman, G., Lärksäter, M., Winblad, B. G., Zetterberg, H., et al. (2008) · Annals of Neurology · doi:10.1002/ana.21345 · Cited by 133 · see citing works
Santana, S., Recuero, M., Bullido, M. J., Valdivieso, F., & Aldudo, J. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.12.010 · Cited by 131 · see citing works
Qi, L., Ke, L., Liu, X., Liao, L., Ke, S., Liu, X., Wang, Y., Lin, X., Zhou, Y., Wu, L., et al. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.04.052 · Cited by 128 · see citing works
McClean, P. L., Jalewa, J., & Hölscher, C. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.07.024 · Cited by 125 · see citing works
How Thalidomide Works Against Cancer
Stewart, A. K. (2014) · Science · doi:10.1126/science.1249543 · Cited by 125 · see citing works
Greig, N. H., Sambamurti, K., Yu, Q.-S., Brossi, A. R., Bruinsma, G., & Lahiri, D. K. (2005) · Current Alzheimer Research · doi:10.2174/1567205054367829 · Cited by 122 · see citing works
Zambrano, Á., Solís, L., Salvadores, N., Cortés, M., Lerchundi, R., & Carola Otth, L. (2008) · Journal of Alzheimer s Disease · doi:10.3233/jad-2008-14301 · Cited by 120 · see citing works
Čulman, J., Blume, A., Gohlke, P., & Unger, T. (2002) · Journal of Human Hypertension · doi:10.1038/sj.jhh.1001442 · Cited by 114 · see citing works
H-Series Protein Kinase Inhibitors and Potential Clinical Applications
Ono-Saito, N., Niki, I., & Hidaka, H. (1999) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(98)00070-9 · Cited by 108 · see citing works
Central Angiotensin II Stimulation Promotes β Amyloid Production in Sprague Dawley Rats
Zhu, D., Shi, J., Zhang, Y., Wang, B., Liu, W., Chen, Z., & Tong, Q. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016037 · Cited by 107 · see citing works
Peripheral delivery of a ROCK inhibitor improves learning and working memory.
Huentelman, M. J., Stephan, D. A., Talboom, J. S., Corneveaux, J. J., Reiman, D., Gerber, J. D., Barnes, C. A., Alexander, G. E., Reiman, E. M., & Bimonte‐Nelson, H. A. (2009) · Behavioral Neuroscience · doi:10.1037/a0014260 · Cited by 107 · see citing works
β2‐adrenoceptor agonists and antagonists and risk of Parkinson's disease
Gronich, N., Abernethy, D. R., Auriel, E., Lavi, I., Rennert, G., & Saliba, W. (2018) · Movement Disorders · doi:10.1002/mds.108 · Cited by 107 · see citing works
Rho Kinase Inhibitor Fasudil Protects againstβ-Amyloid-Induced Hippocampal Neurodegeneration in Rats
Song, Y., Chen, X., Wang, L., Gao, W. Q., & Zhu, M.-J. (2013) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12116 · Cited by 106 · see citing works
A role for APP in Wnt signalling links synapse loss with β-amyloid production
Elliott, C., Rojo, A. I., Ribé, E. M., Broadstock, M., Xia, W., Morin, P., Semënov, M. V., Baillie, G. S., Cuadrado, A., Al‐Shawi, R., et al. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0231-6 · Cited by 106 · see citing works
Self-citationAmyloid β synaptotoxicity is Wnt‐PCP dependent and blocked by fasudil
Sellers, K. J., Elliott, C., Jackson, J. D., Ghosh, A., Ribé, E. M., Rojo, A. I., Jarosz-Griffiths, H., Watson, I. A., Xia, W., Semënov, M. V., et al. (2017) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2017.09.008 · Cited by 104 · see citing works
AbdAlla, S., Langer, A., Fu, X., & Quitterer, U. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms140816917 · Cited by 100 · see citing works
Wang, X. H., Li, L., Hölscher, C., Pan, Y. F., Chen, X. R., & Qi, J. S. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.08.028 · Cited by 99 · see citing works
Kume, K., Hanyu, H., Sakurai, H., Takada, Y., Onuma, T., & Iwamoto, T. (2011) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2011.00746.x · Cited by 99 · see citing works
Marutle, A., Ohmitsu, M., Nilbratt, M., Greig, N., Nordberg, A., & Sugaya, K. (2007) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0705346104 · Cited by 99 · see citing works
Central angiotensin II‐induced Alzheimer‐like tau phosphorylation in normal rat brains
Tian, M., Zhu, D., Xie, W., & Shi, J. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.09.004 · Cited by 97 · see citing works
Li, L., Zhang, Z., Hölscher, C., Gao, C., Jiang, Y., & Liu, Y. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.11.005 · Cited by 93 · see citing works
Xiong, H., Chen, Z., Wang, J., Song, J., Zhao, G., Shen, H., & Deng, Y. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130584 · Cited by 90 · see citing works
Hargis, K. E., & Blalock, E. M. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.05.007 · Cited by 90 · see citing works
Economic analysis of opportunities to accelerate Alzheimer's disease research and development
Scott, T. J., O’Connor, A. C., Link, A. N., & Beaulieu, T. J. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12417 · Cited by 87 · see citing works
β2‐adrenoreceptor medications and risk of Parkinson disease
Nielsen, S. S., Gross, A., Camacho‐Soto, A., Willis, A. W., & Racette, B. A. (2018) · Annals of Neurology · doi:10.1002/ana.25341 · Cited by 86 · see citing works
Alzheimer disease risk genes: 29 and counting
Bertram, L., & Tanzi, R. E. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-019-0158-4 · Cited by 84 · see citing works
Devanand, D. P., Andrews, H., Kreisl, W. C., Razlighi, Q. R., Gershon, A. A., Stern, Y., Mintz, A., Wısnıewskı, T., Acosta, E. P., Pollina, J., et al. (2020) · BMJ Open · doi:10.1136/bmjopen-2019-032112 · Cited by 83 · see citing works
Royea, J., Zhang, L., Tong, X., & Hamel, É. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0329-17.2017 · Cited by 77 · see citing works
Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients
Judge, A., Garriga, C., Arden, N., Lovestone, S., Prieto‐Alhambra, D., Cooper, C. C., & Edwards, C. J. (2017) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2017.10.002 · Cited by 76 · see citing works
Haroutunian, V. H., Greig, N. H., Pei, X., Utsuki, T., Gluck, R., Acevedo, L. D., Davis, K. L., & Wallace, W. (1997) · Molecular Brain Research · doi:10.1016/s0169-328x(96)00297-5 · Cited by 75 · see citing works
The Role of GLP-1 in Neuronal Activity and Neurodegeneration
Hölscher, C. (2010) · Vitamins & Hormones · doi:10.1016/b978-0-12-381517-0.00013-8 · Cited by 74 · see citing works
Kehoe, P., & Passmore, P. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-111376 · Cited by 73 · see citing works
Repurposing of the β-Lactam Antibiotic, Ceftriaxone for Neurological Disorders: A Review
Yimer, E. M., Hishe, H. Z., & Tuem, K. B. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00236 · Cited by 72 · see citing works
Phenserine Efficacy in Alzheimer's Disease
Winblad, B. G., Giacobini, E., Frölich, L., Friedhoff, L. T., Bruinsma, G., Becker, R. E., & Greig, N. H. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-101311 · Cited by 69 · see citing works
Williams, G. H., Gatt, A. P., Clarke, E. E., Corcoran, J. P. T., Doherty, P., Chambers, D. J., & Ballard, C. G. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0555-x · Cited by 69 · see citing works
Self-citationWharton, W., Stein, J., Korcarz, C., Sachs, J. F., Olson, S. R., Zetterberg, H., Dowling, M., Ye, S.-Y., Gleason, C., Underbakke, G., et al. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2012-120763 · Cited by 68 · see citing works
Williams, G. H. (2012) · BMC Genomics · doi:10.1186/1471-2164-13-12 · Cited by 64 · see citing works
Self-citationHou, Y., Zhou, L., Yang, Q. D., Du, X., Li, M., Yuan, M., & Zhou, Z. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.10.030 · Cited by 62 · see citing works
Ali, M. R. A., Abo‐Youssef, A. M., Messiha, B. A. S., & Khattab, M. M. (2016) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-016-1234-6 · Cited by 62 · see citing works
Couch, B. A., DeMarco, G. J., Gourley, S. L., & Koleske, A. J. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-091114 · Cited by 50 · see citing works
Lerchundi, R., Neira, R., Valdivia, S., Vío, K., Concha, M. I., Zambrano, Á., & Carola Otth, L. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-101386 · Cited by 50 · see citing works
Fibroblast growth factor 20 is protective towards dopaminergic neurons in vivo in a paracrine manner
Boshoff, E. L., Fletcher, E. J. R., & Duty, S. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.04.017 · Cited by 46 · see citing works
Lecca, D., Bader, M., Tweedie, D., Hoffman, A. F., Jung, Y. J., Hsueh, S., Hoffer, B. J., Becker, R. E., Pick, C. G., Lupica, C. R., et al. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104528 · Cited by 45 · see citing works
SPIEDw: a searchable platform-independent expression database web tool
Williams, G. H. (2013) · BMC Genomics · doi:10.1186/1471-2164-14-765 · Cited by 44 · see citing works
Self-citationMultitarget Therapeutic Effect of Fasudil in APP/PS1transgenic Mice
Yu, J., Lǐ, Y., Liu, C., Wang, Q., Gu, Q., Wang, H., Zhang, G., Xiao, B., & Ma, C. (2017) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527315666160711104719 · Cited by 44 · see citing works
de Oliveira, F. F., Bertolucci, P. H. F., Chen, E., & Smith, M. D. A. C. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132189 · Cited by 43 · see citing works
Murdoch, D., & Plosker, G. L. (2006) · Drugs · doi:10.2165/00003495-200666050-00009 · Cited by 43 · see citing works
Efficient treatment of Parkinson’s disease using ultrasonography-guided rhFGF20 proteoliposomes
Niu, J., Xie, J.-J., Guo, K., Zhang, X., Xia, F., Zhao, X., Song, L., Zhuge, D., Li, X., Zhao, Y., et al. (2018) · Drug Delivery · doi:10.1080/10717544.2018.1482972 · Cited by 42 · see citing works
Emerging treatments for Alzheimer’s disease for non-amyloid and non-tau targets
Khan, A., Corbett, A., & Ballard, C. G. (2017) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2017.1326818 · Cited by 42 · see citing works
Self-citationPractical Issues in Stem Cell Therapy for Alzheimers Disease
Sugaya, K., Kwak, Y., Ohmitsu, O., Marutle, A., Greig, N. H., & Choumrina, E. (2007) · Current Alzheimer Research · doi:10.2174/156720507781788936 · Cited by 41 · see citing works
Tweedie, D., Fukui, K., Li, Y., Yu, Q.-S., Barak, S., Tamargo, I. A., Rubovitch, V., Holloway, H. W., Lehrmann, E., Wood, W. H., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0156493 · Cited by 40 · see citing works
(−)-Phenserine inhibits neuronal apoptosis following ischemia/reperfusion injury
Chang, C.-F., Lai, J.-H., Wu, J. C.-C., Greig, N. H., Becker, R. E., Luo, Y., Chen, Y., Kang, S.-J., Chiang, Y. H., & Chen, K. (2017) · Brain Research · doi:10.1016/j.brainres.2017.09.015 · Cited by 38 · see citing works
Abdalla, S., Hakim, A. S. E., Abdelbaset, A., el Faramawy, Y., & Quitterer, U. (2015) · BioMed Research International · doi:10.1155/2015/917156 · Cited by 37 · see citing works
Kehoe, P. G., Blair, P. S., Howden, B., Thomas, D. L., Malone, I. B., Horwood, J., Clement, C., Selman, L. E., Baber, H., Lane, A., et al. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-170101 · Cited by 35 · see citing works
Papadopoulos, P., Tong, X., Imboden, H., & Hamel, É. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16658489 · Cited by 35 · see citing works
Patel, N., Spangler, E. L., Greig, N. H., Yu, Q., Ingram, D. K., & Meyer, R. C. (1998) · Neuroreport · doi:10.1097/00001756-199801050-00035 · Cited by 27 · see citing works
Fletcher, E. J. R., Jamieson, A. D., Williams, G. H., Doherty, P., & Duty, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-44803-1 · Cited by 26 · see citing works
Self-citationThe Perils of Alzheimers Drug Development
Schneider, L. S. S., & Lahiri, D. K. (2009) · Current Alzheimer Research · doi:10.2174/156720509787313871 · Cited by 22 · see citing works
Becker, R. E., Greig, N. H., Lahiri, D. K., Bledsoe, J. R., Majercik, S. D., Ballard, C. G., Aarsland, D., Schneider, L. S. S., Flanagan, D. R., Govindarajan, R., et al. (2018) · Current Alzheimer Research · doi:10.2174/1567205015666180110120026 · Cited by 19 · see citing works
Self-citationSeyb, K. I., Schuman, E., Ni, J., et al. (2008) · SLAS DISCOVERY · doi:10.1177/1087057108323909 · Cited by 17 · see citing works
Pfizer abandons research into Alzheimer’s and Parkinson’s diseases
Hawkes, N. (2018) · BMJ · doi:10.1136/bmj.k122 · Cited by 15 · see citing works
Kamei, S., Oishi, M., & Takasu, T. (1996) · Clinical Neuropharmacology · doi:10.1097/00002826-199619050-00006 · Cited by 15 · see citing works
Lahiri, D. K., Alley, G. M., Tweedie, D., et al. (2007) · NeuroMolecular Medicine · doi:10.1007/bf02685889 · Cited by 13 · see citing works
Losartan-Induced Hypotension Leads to Tau Hyperphosphorylation and Memory Deficit
Liu, X.-H., Wang, Z.-H., Xia, Y., Yu, G., Zeng, K., Luo, H.-B., Hu, J.-C., Gong, C., Wang, J.-Z., Zhou, X.-W., et al. (2014) · Journal of Alzheimer's Disease · doi:10.3233/jad-131679 · Cited by 11 · see citing works
Alzheimer’s Disease Progression in the 5×FAD Mouse Captured with a Multiplex Gene Expression Array
Gatt, A. P., Whitfield, D., Ballard, C. G., Doherty, P., & Williams, G. H. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190805 · Cited by 8 · see citing works
Self-citationBallard, C. G., Creese, B., Gatt, A. P., Doherty, P., Francis, P. T., Whitfield, D., Corbett, A., Corcoran, J., Hanger, D. P., Thuret, S., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/622308 · Cited by 7 · see citing works
Self-citationKim, S.-W., Kyu-Jin, C., Park, J., Yoon, S., & Lee, J.-K. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.02.018 · Cited by 6 · see citing works
Zhou, G. (2011) · Journal of Clinical Medicine in Practice · Cited by 5 · see citing works
Ballard, C. G., & Murphy, C. (2018) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2018.06.2419 · Cited by 4 · see citing works
Self-citationLitwack, G. (2010) · Vitamins and hormones · doi:10.1016/b978-0-12-381517-0.00021-7 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 9
- [46]US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02085265 (2020). 28792816
- [47]US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02646982 (2020). 28792816
- [50]Holscher C in Vitamins and Hormones: Incretins and Insulin Secretion (ed. Litwack G) 331– 354 (Academic Press, 2010). 21094894
- [64]US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT01843075 (2019). 28792816
- [73]Killick R, Ballard C, Aarsland D & Sultana J Fasudil for the treatment of Alzheimer’s disease. Preprint at OSF https://osf.io/3e4y6 (2020).
- [107]Sultana J & Ballard C Disease-modifying agents for rheumatoid arthritis: methotrexate, chloroquine phosphate/proguanil hydrochloride, cyclosporine, cyclophosphamide, hydroxychloroquine sulphate, sodium aurothiomalate, and sulfasalazine as potential repurposing treatments for Alzheimer’s Disease; a comprehensive literature review. Preprint at OSF https://mfr.osf.io/render?url=https%3A%2F%2Fosf.io%2F6g57a%2Fdownload (2020).
- [138]US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT02997982 (2020). 28792816
- [139]US National Library of Medicine. ClinicalTrials.gov https://clinicaltrials.gov/ct2/show/NCT03282916 (2020). 28792816
- [143]Sultana J & Ballard C ACE inhibitors: captopril, ramipril, lisinopril, perindopril as potential repurposing treatments for Alzheimer’s disease; a comprehensive literature review. Preprint at OSF https://mfr.osf.io/render?url=https%3A%2F%2Fosf.io%2Fz9uc4%2Fdownload (2020).
Cited by
Sorted by citations
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
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 · see citing works
Iyaswamy, A., Thakur, A., Guan, X.-J., Krishnamoorthi, S., Fung, T. Y., Lu, K., Gaurav, I., Yang, Z., Su, C.-F., Lau, K.-F., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01657-4 · Cited by 134 · see citing works
Enhancing autophagy in Alzheimer's disease through drug repositioning
Eshraghi, M., Ahmadi, M., Afshar, S., Lorzadeh, S., Adlimoghaddam, A., Rezvani Jalal, N., West, R., Dastghaib, S., Igder, S., Torshizi, S. R. N., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108171 · Cited by 89 · see citing works
Cheng, F., Wang, F., Tang, J., Zhou, Y., Fu, Z., Zhang, P., Haines, J. L., Leverenz, J. B., Gan, L., Hu, J., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101379 · Cited by 63 · see citing works
Self-citationWu, Y., Chen, Q., Wen, B., Wu, N., He, B., & Chen, J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.640758 · Cited by 54 · see citing works
Mechanistic Insights for Drug Repurposing and the Design of Hybrid Drugs for Alzheimer’s Disease
Padhi, D., & Govindaraju, T. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00335 · Cited by 47 · see citing works
Artificial intelligence for dementia prevention
Newby, D., Orgeta, V., Marshall, C. R., Lourida, I., Albertyn, C. P., Tamburin, S., Raymont, V., Veldsman, M., Koychev, I., Bauermeister, S., et al. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13463 · Cited by 42 · see citing works
AbuAlrob, M. A., Itbaisha, A., Abujwaid, Y. K., Abulehia, A., Hussein, A., & Mesraoua, B. (2025) · Journal of Alzheimer's Disease Reports · doi:10.1177/25424823251388650 · Cited by 10 · see citing works
Lu, W., Kawatani, K., Ren, Y., Nambara, T., Jia, L., Jeevaratnam, S., Lee, E., Martinez, P. R., Izhar, T., Wang, N., et al. (2026) · Alzheimer's Research & Therapy · doi:10.1186/s13195-026-01982-0 · Cited by 4 · see citing works
- Authors
- Ballard, C., Aarsland, D., Cummings, J., O’Brien, J., Mills, R., Molinuevo, J. L., Fladby, T., Williams, G., Doherty, P., Corbett, A., & Sultana, J.
- Affiliations
- University of Exeter (GB)
- King's College London (GB)
- Cleveland Clinic (US)
- University of Oslo (NO)
- University of Messina (IT)
- Corresponding author
- Ballard, Clive
- ORCID
- Venue
- Nature Reviews Neurology
- Published
- 2020-09-16
- Volume
- 16
- Issue
- 12
- Pages
- 661-673
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC8291993
- OpenAlex
- W3046419426
- Cited by
- 201
- References
- 132
- Citations by year
- 2026: 17 · 2025: 38 · 2024: 46 · 2023: 32 · 2022: 33 · 2021: 34 · 2020: 1
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Open Research Exeter (University of Exeter) (acceptedVersion)
- Figshare (submittedVersion)
- Royal Devon and Exeter Research Repository (Royal Devon and Exeter) (submittedVersion)
- Funders
- Wellcome Trust
- National Institute on Aging (R01AG053798, P20AG068053)
- National Institute of General Medical Sciences (P20GM109025)
- National Institute of Neurological Disorders and Stroke (U01NS093334)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- drug repurposing, Alzheimer's disease, mild cognitive impairment, gene expression profiling, Delphi consensus, microglia, neurons
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Humans, Randomized Controlled Trials as Topic, Consensus, Drug Repositioning, Cognitive Dysfunction
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