A Review of the pharmacological treatments of Alzheimer’s disease (AD)
DOI:
https://doi.org/10.47611/jsrhs.v11i3.3475Keywords:
Alzheimer’s disease, Pharmacological treatments, Review articleAbstract
Alzheimer’s disease (AD) is an irreversible, neurodegenerative disease that has haunted millions of lives globally. This article briefly reviews the diagnosis and pathophysiology behind AD while focusing on the currently approved and potential pharmacological treatments for AD. Cholinesterase inhibitors and NMDA receptor antagonists have been the most widely used drug to treat AD for decades. In 2003, Aducanumab was authorized by the US FDA for market use but not by other countries. Unfortunately, all the drugs mentioned could only ameliorate the clinical syndromes of AD instead of curing the disease and came with various side effects. Research has shown that the clinical progression of AD happens in parallel with the accumulation of amyloid β plaques and the spread of neurofibrillary tangles composed of hyperphosphorylated tau. There are many potential drugs under different stages of trials, including β‑secretase inhibitors, γ‑secretase inhibitors, monoclonal antibodies, tau aggregation inhibitors, and other therapeutic strategies. Although they are still immature to be put into clinical use, we are looking forward that a specific and efficient drug that has fewer side effects for AD will be developed in the future.
Downloads
References or Bibliography
AlirezaAtriMD, P. (2019). The Alzheimer’s Disease Clinical Spectrum: Diagnosis and Management. Medical Clinics of North America, 103(2), 263-293. https://doi.org/https://doi.org/10.1016/j.mcna.2018.10.009
Alzforum. (2019a). Ladostigil https://www.alzforum.org/therapeutics/ladostigil
Alzforum. (2019b). End of the BACE Inhibitors? Elenbecestat Trials Halted Amid Safety Concerns https://www.alzforum.org/news/research-news/end-bace-inhibitors-elenbecestat-trials-halted-amid-safety-concerns
Alzheimer's Disease International, M. U. (2021). World Alzheimer Report 2021. https://www.alzint.org/resource/world-alzheimer-report-2021/
Athar, T., Al Balushi, K., & Khan, S. A. (2021). Recent advances on drug development and emerging therapeutic agents for Alzheimer’s disease. Molecular Biology Reports, 48(7), 5629-5645. https://doi.org/10.1007/s11033-021-06512-9
Atri, A., Frölich, L., Ballard, C., Tariot, P. N., Molinuevo, J. L., Boneva, N., Windfeld, K., Raket, L. L., & Cummings, J. L. (2018). Effect of Idalopirdine as Adjunct to Cholinesterase Inhibitors on Change in Cognition in Patients With Alzheimer Disease. JAMA, 319(2), 130. https://doi.org/10.1001/jama.2017.20373
Birks, J. S., & Harvey, R. J. (2018). Donepezil for dementia due to Alzheimer's disease. Cochrane Database of Systematic Reviews, 2018(6). https://doi.org/10.1002/14651858.cd001190.pub3
Blume, T., Filser, S., Jaworska, A., Blain, J.-F., Koenig, G., Moschke, K., Lichtenthaler, S. F., & Herms, J. (2018). BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines [Original Research]. Frontiers in Aging Neuroscience, 10. https://doi.org/10.3389/fnagi.2018.00229
Briggs, R., Kennelly, S. P., & O'Neill, D. (2016). Drug treatments in Alzheimer’s disease. Clinical Medicine, 16(3), 247-253. https://doi.org/10.7861/clinmedicine.16-3-247
Chandra, A., Dervenoulas, G., & Politis, M. (2019). Magnetic resonance imaging in Alzheimer’s disease and mild cognitive impairment. Journal of Neurology, 266(6), 1293-1302. https://doi.org/10.1007/s00415-018-9016-3
Dennis J Selkoe, J. H. (2016). The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Molecular Medicine 8(6), 595-608. https://doi.org/10.15252/emmm.201606210
Dhillon, S. (2021). Aducanumab: First Approval. Drugs, 81(12), 1437-1443. https://doi.org/10.1007/s40265-021-01569-z
Doody, R. S., Raman, R., Farlow, M., Iwatsubo, T., Vellas, B., Joffe, S., Kieburtz, K., He, F., Sun, X., Thomas, R. G., Aisen, P. S., Siemers, E., Sethuraman, G., & Mohs, R. (2013). A Phase 3 Trial of Semagacestat for Treatment of Alzheimer's Disease. New England Journal of Medicine, 369(4), 341-350. https://doi.org/10.1056/nejmoa1210951
Cavazzoni, P, D., FDA Center for Drug Evaluation and Research. (2021). FDA’s Decision to Approve New Treatment for Alzheimer’s Disease. Retrieved 07/17 from https://www.fda.gov/drugs/news-events-human-drugs/fdas-decision-approve-new-treatment-alzheimers-disease
Folch, J., Petrov, D., Ettcheto, M., Abad, S., Sánchez-López, E., García, M. L., Olloquequi, J., Beas-Zarate, C., Auladell, C., & Camins, A. (2016). Current Research Therapeutic Strategies for Alzheimer’s Disease Treatment. Neural Plasticity, 2016, 1-15. https://doi.org/10.1155/2016/8501693
Ghosh, A. K., & Tang, J. (2015). Prospects of β-Secretase Inhibitors for the Treatment of Alzheimer’s Disease. ChemMedChem, 10(9), 1463-1466. https://doi.org/10.1002/cmdc.201500216
Green Valley (Shanghai) Pharmaceuticals Co., L. (2021). A Study of Sodium Oligomannate (GV-971) in Participants With Mild to Moderate Alzheimer's Disease (GREEN MEMORY) https://clinicaltrials.gov/ct2/show/NCT04520412
Hey, J. A., Kocis, P., Hort, J., Abushakra, S., Power, A., Vyhnálek, M., Yu, J. Y., & Tolar, M. (2018). Discovery and Identification of an Endogenous Metabolite of Tramiprosate and Its Prodrug ALZ-801 that Inhibits Beta Amyloid Oligomer Formation in the Human Brain. CNS Drugs, 32(9), 849-861. https://doi.org/10.1007/s40263-018-0554-0
Keating, D. M. R. G. M. (2006). Memantine：A Review of its Use in Alzheimer’s Disease. Drugs, 66, 1515-1534. https://link.springer.com/article/10.2165/00003495-200666110-00015#citeas
Lane, C. A., Hardy, J., & Schott, J. M. (2018). Alzheimer's disease. European Journal of Neurology, 25(1), 59-70. https://doi.org/10.1111/ene.13439
Long, J. M., & Holtzman, D. M. (2019). Alzheimer Disease: An Update on Pathobiology and Treatment Strategies. Cell, 179(2), 312-339. https://doi.org/10.1016/j.cell.2019.09.001
Mangialasche, F., Solomon, A., Winblad, B., Mecocci, P., & Kivipelto, M. (2010). Alzheimer's disease: clinical trials and drug development. The Lancet Neurology, 9(7), 702-716. https://doi.org/10.1016/S1474-4422(10)70119-8
Marta Cortes-Canteli , C. I. (2020). Alzheimer's Disease and Vascular Aging: JACC Focus Seminar. Journal of the American College of Cardiology, 75(8), 942-951. https://doi.org/10.1016/j.jacc.2019.10.062
McShane, R., Westby, M. J., Roberts, E., Minakaran, N., Schneider, L., Farrimond, L. E., Maayan, N., Ware, J., & Debarros, J. (2019). Memantine for dementia. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.cd003154.pub6
Mufson, E. J., Counts, S. E., Perez, S. E., & Ginsberg, S. D. (2008). Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications. Expert Review of Neurotherapeutics, 8(11), 1703-1718. https://doi.org/10.1586/14737175.8.11.1703
Reitz, C. (2015). Genetic diagnosis and prognosis of Alzheimer’s disease: challenges and opportunities. Expert Review of Molecular Diagnostics, 15(3), 339-348. https://doi.org/10.1586/14737159.2015.1002469
Rhodius-Meester, H. F. M., Van Maurik, I. S., Koikkalainen, J., Tolonen, A., Frederiksen, K. S., Hasselbalch, S. G., Soininen, H., Herukka, S.-K., Remes, A. M., Teunissen, C. E., Barkhof, F., Pijnenburg, Y. A. L., Scheltens, P., Lötjönen, J., & Van Der Flier, W. M. (2020). Selection of memory clinic patients for CSF biomarker assessment can be restricted to a quarter of cases by using computerized decision support, without compromising diagnostic accuracy. PLOS ONE, 15(1), e0226784. https://doi.org/10.1371/journal.pone.0226784
Scheltens, P., De Strooper, B., Kivipelto, M., Holstege, H., Chételat, G., Teunissen, C. E., Cummings, J., & Van Der Flier, W. M. (2021). Alzheimer's disease. The Lancet, 397(10284), 1577-1590. https://doi.org/10.1016/s0140-6736(20)32205-4
Sochocka, M., Ochnik, M., Sobczyński, M., Siemieniec, I., Orzechowska, B., Naporowski, P., & Leszek, J. (2019). New therapeutic targeting of Alzheimer’s disease with the potential use of proline-rich polypeptide complex to modulate an innate immune response - preliminary study. Journal of Neuroinflammation, 16(1). https://doi.org/10.1186/s12974-019-1520-6
Sperling, R., Henley, D., Aisen, P. S., Raman, R., Donohue, M. C., Ernstrom, K., Rafii, M. S., Streffer, J., Shi, Y., Karcher, K., Raghavan, N., Tymofyeyev, Y., Bogert, J., Brashear, H. R., Novak, G., Thipphawong, J., Saad, Z. S., Kolb, H., Rofael, H., . . . Romano, G. (2021). Findings of Efficacy, Safety, and Biomarker Outcomes of Atabecestat in Preclinical Alzheimer Disease. JAMA Neurology, 78(3), 293. https://doi.org/10.1001/jamaneurol.2020.4857
Stephen R Robinson 1, G. M. B., Hyoung-Gon Lee, Gerald Münch. (2004). Lessons from the AN 1792 Alzheimer vaccine: lest we forget. Neurobiology of Aging, 25(5), 609-615. https://doi.org/https://doi.org/10.1016/j.neurobiolaging.2003.12.020
Thiratmatrakul, S., Yenjai, C., Waiwut, P., Vajragupta, O., Reubroycharoen, P., Tohda, M., & Boonyarat, C. (2014). Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease. Eur J Med Chem, 75, 21-30. https://doi.org/10.1016/j.ejmech.2014.01.020
Weller, J., & Budson, A. (2018). Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Research, 7, 1161. https://doi.org/10.12688/f1000research.14506.1
Yiannopoulou, K. G., & Papageorgiou, S. G. (2013). Current and future treatments for Alzheimer’s disease. Therapeutic Advances in Neurological Disorders, 6(1), 19-33. https://doi.org/10.1177/1756285612461679
Published
How to Cite
Issue
Section
Copyright (c) 2022 Derrick Feng Jiang; Dr Xiao
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright holder(s) granted JSR a perpetual, non-exclusive license to distriute & display this article.
