Abstract
Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aβ (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.
[http://dx.doi.org/10.1038/nature19323] [PMID: 27582220]
[http://dx.doi.org/10.3389/fnmol.2020.609073] [PMID: 33324164]
[http://dx.doi.org/10.1038/s41598-018-24501-0] [PMID: 29686315]
[http://dx.doi.org/10.1038/nature22809] [PMID: 28640269]
[http://dx.doi.org/10.3233/HAB-160306] [PMID: 28035915]
[http://dx.doi.org/10.1074/jbc.M117.801514] [PMID: 28924036]
[http://dx.doi.org/10.1038/78682] [PMID: 10932230]
[http://dx.doi.org/10.1001/jama.2021.3854] [PMID: 33783469]
[http://dx.doi.org/10.1002/alz.12235] [PMID: 33135288]
[http://dx.doi.org/10.1111/hex.12876] [PMID: 30809895]
[http://dx.doi.org/10.1002/alz.047259]
[http://dx.doi.org/10.1016/j.jalz.2018.02.018] [PMID: 29653606]
[http://dx.doi.org/10.1126/science.1566067] [PMID: 1566067]
[PMID: 29181491]
[http://dx.doi.org/10.1002/prot.25978] [PMID: 32666627]
[http://dx.doi.org/10.1016/j.trci.2016.06.002] [PMID: 29067304]
[http://dx.doi.org/10.1002/psp4.12224] [PMID: 28653357]
[http://dx.doi.org/10.1001/jamaneurol.2021.4161] [PMID: 34807243]
[http://dx.doi.org/10.1002/14651858.CD001190.pub3]
[http://dx.doi.org/10.3389/fnins.2019.00472] [PMID: 31156366]
[http://dx.doi.org/10.1038/nm1234] [PMID: 15834427]
[http://dx.doi.org/10.1016/S0140-6736(04)16499-4] [PMID: 15220031]
[http://dx.doi.org/10.1016/S1474-4422(15)00258-6] [PMID: 26515660]
[http://dx.doi.org/10.1002/14651858.CD003154.pub6]
[PMID: 34585212]
[http://dx.doi.org/10.1038/nm840] [PMID: 12640446]
[http://dx.doi.org/10.1056/NEJMoa2100708] [PMID: 33720637]
[http://dx.doi.org/10.1038/s43587-021-00070-2] [PMID: 37117834]
[http://dx.doi.org/10.7573/dic.2021-7-3] [PMID: 34650610]
[http://dx.doi.org/10.1001/jamainternmed.2021.4607] [PMID: 34254984]
[http://dx.doi.org/10.1136/bmj.n1503]
[http://dx.doi.org/10.1097/01.NT.0000725248.82870.33]
[http://dx.doi.org/10.1016/j.bcp.2020.113945] [PMID: 32247851]
[http://dx.doi.org/10.1016/S2215-0366(21)00197-8] [PMID: 34087114]
[http://dx.doi.org/10.1002/advs.202201740] [PMID: 35851766]
[http://dx.doi.org/10.1038/d41586-021-01546-2] [PMID: 34103732]
[http://dx.doi.org/10.1097/YCO.0000000000000587] [PMID: 32040044]
[http://dx.doi.org/10.1186/1742-4933-10-18] [PMID: 23663286]
[http://dx.doi.org/10.1111/ene.14484] [PMID: 32808453]
[http://dx.doi.org/10.1155/2022/9343514] [PMID: 35308835]
[http://dx.doi.org/10.3233/JAD-160122] [PMID: 27031492]
[http://dx.doi.org/10.1002/alz.12155] [PMID: 32808733]
[http://dx.doi.org/10.3233/ADR-190143] [PMID: 32206755]
[http://dx.doi.org/10.1038/nature25456] [PMID: 29420472]
[http://dx.doi.org/10.1038/s41582-021-00557-x] [PMID: 34535787]
[http://dx.doi.org/10.3389/fncel.2015.00191] [PMID: 26074767]
[http://dx.doi.org/10.15252/emmm.201606210] [PMID: 27025652]
[http://dx.doi.org/10.1039/C8RA03620A] [PMID: 35540246]
[http://dx.doi.org/10.1016/j.jalz.2011.05.2024]
[http://dx.doi.org/10.1515/revneuro-2017-0063] [PMID: 29447116]
[http://dx.doi.org/10.1016/j.bbrc.2016.09.062] [PMID: 27639648]
[http://dx.doi.org/10.1159/000511506] [PMID: 33321511]
[http://dx.doi.org/10.1016/j.tips.2013.03.002] [PMID: 23582316]
[http://dx.doi.org/10.1073/pnas.1218402110] [PMID: 23703910]
[http://dx.doi.org/10.1038/s41594-020-0505-6] [PMID: 32989305]
[http://dx.doi.org/10.1063/1.5133635] [PMID: 32007046]
[http://dx.doi.org/10.1039/C4CP05563B] [PMID: 25719972]
[http://dx.doi.org/10.1016/j.arr.2021.101339] [PMID: 33831607]
[http://dx.doi.org/10.1186/s13195-021-00838-z] [PMID: 33971962]
[http://dx.doi.org/10.1038/s41582-019-0295-9] [PMID: 31784690]
[http://dx.doi.org/10.1002/acn3.469] [PMID: 29296624]
[http://dx.doi.org/10.1523/JNEUROSCI.0420-17.2017] [PMID: 28446659]
[http://dx.doi.org/10.1523/JNEUROSCI.2080-16.2016] [PMID: 27810931]
[http://dx.doi.org/10.1002/alz.12286] [PMID: 33656288]
[http://dx.doi.org/10.1002/alz.12213] [PMID: 33135381]