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Review Article

Aducanumab in Alzheimer’s Disease: A Critical Update

Author(s): Sumel Ashique, Ekta Sirohi, Shubneesh Kumar, Mohd Rihan, Neeraj Mishra, Shvetank Bhatt, Rupesh K. Gautam, Sachin Kumar Singh, Gaurav Gupta*, Dinesh Kumar Chellappan and Kamal Dua*

Volume 31, Issue 31, 2024

Published on: 22 September, 2023

Page: [5004 - 5026] Pages: 23

DOI: 10.2174/0929867331666230727103553

Price: $65

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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.

Keywords: Aducanumab, amyloid plaque, Alzheimer's disease, anti-N-methyl D-aspartate, anti-cholinesterase, inflammation.

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[1]
Sevigny, J.; Chiao, P.; Bussière, T.; Weinreb, P.H.; Williams, L.; Maier, M.; Dunstan, R.; Salloway, S.; Chen, T.; Ling, Y.; O’Gorman, J.; Qian, F.; Arastu, M.; Li, M.; Chollate, S.; Brennan, M.S.; Quintero-Monzon, O.; Scannevin, R.H.; Arnold, H.M.; Engber, T.; Rhodes, K.; Ferrero, J.; Hang, Y.; Mikulskis, A.; Grimm, J.; Hock, C.; Nitsch, R.M.; Sandrock, A. The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature, 2016, 537(7618), 50-56.
[http://dx.doi.org/10.1038/nature19323] [PMID: 27582220]
[2]
Brown, M.R.; Radford, S.E.; Hewitt, E.W. Modulation of β-amyloid fibril formation in Alzheimer’s disease by microglia and infection. Front. Mol. Neurosci., 2020, 13, 609073.
[http://dx.doi.org/10.3389/fnmol.2020.609073] [PMID: 33324164]
[3]
Arndt, J.W.; Qian, F.; Smith, B.A.; Quan, C.; Kilambi, K.P.; Bush, M.W.; Walz, T.; Pepinsky, R.B.; Bussière, T.; Hamann, S.; Cameron, T.O.; Weinreb, P.H. Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β. Sci. Rep., 2018, 8(1), 6412.
[http://dx.doi.org/10.1038/s41598-018-24501-0] [PMID: 29686315]
[4]
Sevigny, J.; Chiao, P.; Bussière, T.; Weinreb, P.H.; Williams, L.; Maier, M.; Dunstan, R.; Salloway, S.; Chen, T.; Ling, Y.; O’Gorman, J.; Qian, F.; Arastu, M.; Li, M.; Chollate, S.; Brennan, M.S.; Quintero-Monzon, O.; Scannevin, R.H.; Arnold, H.M.; Engber, T.; Rhodes, K.; Ferrero, J.; Hang, Y.; Mikulskis, A.; Grimm, J.; Hock, C.; Nitsch, R.M.; Sandrock, A. Addendum: The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease. Nature, 2017, 546(7659), 564.
[http://dx.doi.org/10.1038/nature22809] [PMID: 28640269]
[5]
Finke, J.M.; Banks, W.A. Modulators of IgG penetration through the blood-brain barrier: Implications for Alzheimer’s disease immunotherapy. Hum. Antibodies, 2017, 25(3-4), 131-146.
[http://dx.doi.org/10.3233/HAB-160306] [PMID: 28035915]
[6]
Zhao, J.; Nussinov, R.; Ma, B. Mechanisms of recognition of amyloid-β (Aβ) monomer, oligomer, and fibril by homologous antibodies. J. Biol. Chem., 2017, 292(44), 18325-18343.
[http://dx.doi.org/10.1074/jbc.M117.801514] [PMID: 28924036]
[7]
Bard, F.; Cannon, C.; Barbour, R.; Burke, R.L.; Games, D.; Grajeda, H.; Guido, T.; Hu, K.; Huang, J.; Johnson- Wood, K.; Khan, K.; Kholodenko, D.; Lee, M.; Lieberburg, I.; Motter, R.; Nguyen, M.; Soriano, F.; Vasquez, N.; Weiss, K.; Welch, B.; Seubert, P.; Schenk, D.; Yednock, T. Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med., 2000, 6(8), 916-919.
[http://dx.doi.org/10.1038/78682] [PMID: 10932230]
[8]
Alexander, G.C.; Emerson, S.; Kesselheim, A.S. Evaluation of aducanumab for Alzheimer disease: Scientific evidence and regulatory review involving efficacy, safety, and futility. JAMA, 2021, 325(17), 1717-1718.
[http://dx.doi.org/10.1001/jama.2021.3854] [PMID: 33783469]
[9]
Sabbagh, M.N.; Cummings, J. Open Peer Commentary to “Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen December 2019”. Alzheimers Dement., 2021, 17(4), 702-703.
[http://dx.doi.org/10.1002/alz.12235] [PMID: 33135288]
[10]
Watson, J.; Saunders, S.; Muniz Terrera, G.; Ritchie, C.; Evans, A.; Luz, S.; Clarke, C. What matters to people with memory problems, healthy volunteers and health and social care professionals in the context of developing treatment to prevent Alzheimer’s dementia? A qualitative study. Health Expect., 2019, 22(3), 504-517.
[http://dx.doi.org/10.1111/hex.12876] [PMID: 30809895]
[11]
Haeberlein, S.B.; von Hehn, C.; Tian, Y.; Chalkias, S.; Muralidharan, K.K.; Chen, T.; Wu, S.; Skordos, L.; Nisenbaum, L.; Rajagovindan, R.; Dent, G.; Harrison, K.; Nestorov, I.; Zhu, Y.; Mallinckrodt, C.; Sandrock, A. Emerge and Engage topline results: Phase 3 studies of aducanumab in early Alzheimer’s disease. Alzheimers Dement., 2020, 16(S9), e047259.
[http://dx.doi.org/10.1002/alz.047259]
[12]
Jack, C.R., Jr; Bennett, D.A.; Blennow, K.; Carrillo, M.C.; Dunn, B.; Haeberlein, S.B.; Holtzman, D.M.; Jagust, W.; Jessen, F.; Karlawish, J.; Liu, E.; Molinuevo, J.L.; Montine, T.; Phelps, C.; Rankin, K.P.; Rowe, C.C.; Scheltens, P.; Siemers, E.; Snyder, H.M.; Sperling, R.; Elliott, C.; Masliah, E.; Ryan, L.; Silverberg, N. NIA-AA research framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement., 2018, 14(4), 535-562.
[http://dx.doi.org/10.1016/j.jalz.2018.02.018] [PMID: 29653606]
[13]
The battle over an Alzheimer’s treatment; Biogen’s promising drug is caught in the FDA’s political and bureaucratic limbo. 2021. Available From: https://www.wsj.com/articles/the-battle-over-an-alzheimers-treatment-11618873596
[14]
Hardy, J.A.; Higgins, G.A. Alzheimer’s disease: The amyloid cascade hypothesis. Science, 1992, 256(5054), 184-185.
[http://dx.doi.org/10.1126/science.1566067] [PMID: 1566067]
[15]
Budd Haeberlein, S.; O’Gorman, J.; Chiao, P.; Bussière, T.; von Rosenstiel, P.; Tian, Y.; Zhu, Y.; von Hehn, C.; Gheuens, S.; Skordos, L.; Chen, T.; Sandrock, A. Clinical development of aducanumab, an Anti-Aβ human monoclonal antibody being investigated for the treatment of early Alzheimer’s disease. J. Prev. Alzheimers Dis., 2017, 4(4), 255-263.
[PMID: 29181491]
[16]
Frost, C.V.; Zacharias, M. From monomer to fibril: Abeta-amyloid binding to Aducanumab antibody studied by molecular dynamics simulation. Proteins, 2020, 88(12), 1592-1606.
[http://dx.doi.org/10.1002/prot.25978] [PMID: 32666627]
[17]
Ferrero, J.; Williams, L.; Stella, H.; Leitermann, K.; Mikulskis, A.; O’Gorman, J.; Sevigny, J. First-in-human, double-blind, placebo-controlled, single-dose escalation study of aducanumab (BIIB037) in mild-to-moderate Alzheimer’s disease. Alzheimers Dement., 2016, 2(3), 169-176.
[http://dx.doi.org/10.1016/j.trci.2016.06.002] [PMID: 29067304]
[18]
Ryman, J.T.; Meibohm, B. Pharmacokinetics of monoclonal antibodies. CPT Pharmacometrics Syst. Pharmacol., 2017, 6(9), 576-588.
[http://dx.doi.org/10.1002/psp4.12224] [PMID: 28653357]
[19]
Salloway, S.; Chalkias, S.; Barkhof, F.; Burkett, P.; Barakos, J.; Purcell, D.; Suhy, J.; Forrestal, F.; Tian, Y.; Umans, K.; Wang, G.; Singhal, P.; Budd Haeberlein, S.; Smirnakis, K. Amyloid-related imaging abnormalities in 2 phase 3 studies evaluating aducanumab in patients with early Alzheimer disease. JAMA Neurol., 2022, 79(1), 13-21.
[http://dx.doi.org/10.1001/jamaneurol.2021.4161] [PMID: 34807243]
[20]
Birks, JS; Harvey, RJ Donepezil for dementia due to Alzheimer's disease. Cochrane Database Syst. Rev., 2018, 6(6), CD001190.
[http://dx.doi.org/10.1002/14651858.CD001190.pub3]
[21]
Li, D.D.; Zhang, Y.H.; Zhang, W.; Zhao, P. Meta-analysis of randomized controlled trials on the efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer’s disease. Front. Neurosci., 2019, 13, 472.
[http://dx.doi.org/10.3389/fnins.2019.00472] [PMID: 31156366]
[22]
Klyubin, I.; Walsh, D.M.; Lemere, C.A.; Cullen, W.K.; Shankar, G.M.; Betts, V.; Spooner, E.T.; Jiang, L.; Anwyl, R.; Selkoe, D.J.; Rowan, M.J. Amyloid β protein immunotherapy neutralizes Aβ oligomers that disrupt synaptic plasticity in vivo. Nat. Med., 2005, 11(5), 556-561.
[http://dx.doi.org/10.1038/nm1234] [PMID: 15834427]
[23]
Courtney, C.; Farrell, D.; Gray, R.; Hills, R.; Lynch, L.; Sellwood, E.; Edwards, S.; Hardyman, W.; Raftery, J.; Crome, P.; Lendon, C.; Shaw, H.; Bentham, P. Long-term donepezil treatment in 565 patients with Alzheimer’s disease (AD2000): Randomised double-blind trial. Lancet, 2004, 363(9427), 2105-2115.
[http://dx.doi.org/10.1016/S0140-6736(04)16499-4] [PMID: 15220031]
[24]
Howard, R.; McShane, R.; Lindesay, J.; Ritchie, C.; Baldwin, A.; Barber, R.; Burns, A.; Dening, T.; Findlay, D.; Holmes, C.; Jones, R.; Jones, R.; McKeith, I.; Macharouthu, A.; O’Brien, J.; Sheehan, B.; Juszczak, E.; Katona, C.; Hills, R.; Knapp, M.; Ballard, C.; Brown, R.G.; Banerjee, S.; Adams, J.; Johnson, T.; Bentham, P.; Phillips, P.P.J. Nursing home placement in the Donepezil and Memantine in Moderate to Severe Alzheimer’s Disease (DOMINO-AD) trial: Secondary and post-hoc analyses. Lancet Neurol., 2015, 14(12), 1171-1181.
[http://dx.doi.org/10.1016/S1474-4422(15)00258-6] [PMID: 26515660]
[25]
McShane, R.; Westby, M.J.; Roberts, E.; Minakaran, N.; Schneider, L.; Farrimond, L.E.; Maayan, N.; Ware, J.; Debarros, J. Memantine for dementia. Cochrane Database Syst Rev., 2019, 3(3), CD003154.
[http://dx.doi.org/10.1002/14651858.CD003154.pub6]
[26]
Cummings, J.; Aisen, P.; Apostolova, L.G.; Atri, A.; Salloway, S.; Weiner, M. Aducanumab: Appropriate use recommendations. J. Prev. Alzheimers Dis., 2021, 8(4), 398-410.
[PMID: 34585212]
[27]
Nicoll, J.A.R.; Wilkinson, D.; Holmes, C.; Steart, P.; Markham, H.; Weller, R.O. Neuropathology of human Alzheimer disease after immunization with amyloid-β peptide: A case report. Nat. Med., 2003, 9(4), 448-452.
[http://dx.doi.org/10.1038/nm840] [PMID: 12640446]
[28]
B. Inc. Single and multiple ascending dose study of aducanumab (BIIB037) in Japanese participants with AD. 2020. Available From: https://clinicaltrials.gov/ct2/show/results/
[29]
L. Biogen Inc and E. Co. A study to assess absolute bioavailability of aducanumab in healthy volunteers. 2021. Available From: https:// clinicaltrials.gov/ct2/show/NCT04924140
[30]
B. Inc. A study of aducanumab in participants with mild cognitive impairment due to AD or with mild AD dementia to evaluate the safety of continued dosing in participants with asymptomatic amyloid-related imaging abnormalities. 2020. Available From: https://clinicaltrials.gov/ct2/ show/NCT03639987
[31]
B. Inc. 221AD302 phase 3 study of aducanumab BIIB037 in early AD. Available From: https://clinicaltrials.gov/ct2/ show/NCT02484547
[32]
B. Inc. A study to evaluate safety and tolerability of aducanumab in participants with AD who had previously participated in the aducanumab studies 221AD103, 221AD301, 221AD302 and 221AD205 2021. Available From: https:// clinicaltrials.gov/ct2/show/NCT04241068
[33]
Mintun, M.A.; Lo, A.C.; Duggan Evans, C.; Wessels, A.M.; Ardayfio, P.A.; Andersen, S.W.; Shcherbinin, S.; Sparks, J.; Sims, J.R.; Brys, M.; Apostolova, L.G.; Salloway, S.P.; Skovronsky, D.M. Donanemab in early Alzheimer’s disease. N. Engl. J. Med., 2021, 384(18), 1691-1704.
[http://dx.doi.org/10.1056/NEJMoa2100708] [PMID: 33720637]
[34]
Novak, P.; Kovacech, B.; Katina, S.; Schmidt, R.; Scheltens, P.; Kontsekova, E.; Ropele, S.; Fialova, L.; Kramberger, M.; Paulenka-Ivanovova, N.; Smisek, M.; Hanes, J.; Stevens, E.; Kovac, A.; Sutovsky, S.; Parrak, V.; Koson, P.; Prcina, M.; Galba, J.; Cente, M.; Hromadka, T.; Filipcik, P.; Piestansky, J.; Samcova, M.; Prenn-Gologranc, C.; Sivak, R.; Froelich, L.; Fresser, M.; Rakusa, M.; Harrison, J.; Hort, J.; Otto, M.; Tosun, D.; Ondrus, M.; Winblad, B.; Novak, M.; Zilka, N. ADAMANT: A placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer’s disease. Nature Aging, 2021, 1(6), 521-534.
[http://dx.doi.org/10.1038/s43587-021-00070-2] [PMID: 37117834]
[35]
Biogen. EMERGE and ENGAGE topline results: Two phase 3 studies to evaluate aducanumab in patients with early Alzheimer’s disease. ClinicalTrials on Alzheimer’s Disease (CTAD). San Diego 2019. Available From: https://investors.biogen.com/static-files/ddd45672-9c7e-4c99-8a06-3b557697c06f
[36]
Tampi, R.R.; Forester, B.P.; Agronin, M. Aducanumab: Evidence from clinical trial data and controversies. Drugs Context, 2021, 10, 1-9.
[http://dx.doi.org/10.7573/dic.2021-7-3] [PMID: 34650610]
[37]
Dunn, B.; Stein, P.; Cavazzoni, P. Approval of aducanumab for Alzheimer disease-the FDA’s perspective. JAMA Intern. Med., 2021, 181(10), 1276-1278.
[http://dx.doi.org/10.1001/jamainternmed.2021.4607] [PMID: 34254984]
[38]
Mahase, E. Three FDA advisory panel members resign over approval of Alzheimer’s drug. BMJ, 2021, 373, n1503.
[http://dx.doi.org/10.1136/bmj.n1503]
[39]
Talan, J. FDA panel votes ‘No’ to approving aducanumab for Alzheimer’s, citing inconsistent data. Neurol. Today, 2020, 20(23), 1,36-38.
[http://dx.doi.org/10.1097/01.NT.0000725248.82870.33]
[40]
Mullane, K.; Williams, M. Alzheimer’s disease beyond amyloid: Can the repetitive failures of amyloid-targeted therapeutics inform future approaches to dementia drug discovery? Biochem. Pharmacol., 2020, 177, 113945.
[http://dx.doi.org/10.1016/j.bcp.2020.113945] [PMID: 32247851]
[41]
Liu, K.Y.; Schneider, L.S.; Howard, R. The need to show minimum clinically important differences in Alzheimer’s disease trials. Lancet Psychiatry, 2021, 8(11), 1013-1016.
[http://dx.doi.org/10.1016/S2215-0366(21)00197-8] [PMID: 34087114]
[42]
Luo, M.; Lee, L.K.C.; Peng, B.; Choi, C.H.J.; Tong, W.Y.; Voelcker, N.H. Delivering the promise of gene therapy with nanomedicines in treating central nervous system diseases. Adv. Sci., 2022, 9(26), 2201740.
[http://dx.doi.org/10.1002/advs.202201740] [PMID: 35851766]
[43]
Mullard, A. Landmark Alzheimer’s drug approval confounds research community. Nature, 2021, 594(7863), 309-310.
[http://dx.doi.org/10.1038/d41586-021-01546-2] [PMID: 34103732]
[44]
Loureiro, J.C.; Pais, M.V.; Stella, F.; Radanovic, M.; Teixeira, A.L.; Forlenza, O.V.; de Souza, L.C. Passive antiamyloid immunotherapy for Alzheimerʼs disease. Curr. Opin. Psychiatry, 2020, 33(3), 284-291.
[http://dx.doi.org/10.1097/YCO.0000000000000587] [PMID: 32040044]
[45]
Moreth, J.; Mavoungou, C.; Schindowski, K. Passive anti-amyloid immunotherapy in Alzheimer’s disease: What are the most promising targets? Immun. Ageing, 2013, 10(1), 18.
[http://dx.doi.org/10.1186/1742-4933-10-18] [PMID: 23663286]
[46]
Gleason, A.; Ayton, S.; Bush, A.I. Unblinded by the light: Amyloid-related imaging abnormalities in Alzheimer’s clinical trials. Eur. J. Neurol., 2021, 28(1), e1.
[http://dx.doi.org/10.1111/ene.14484] [PMID: 32808453]
[47]
Beshir, S.A.; Aadithsoorya, A.M.; Parveen, A.; Goh, S.S.L.; Hussain, N.; Menon, V.B. Aducanumab therapy to Treat Alzheimer’s disease: A narrative review. Int. J. Alzheimers Dis., 2022, 2022, 1-10.
[http://dx.doi.org/10.1155/2022/9343514] [PMID: 35308835]
[48]
Piazza, F.; Winblad, B. Amyloid-Related Imaging Abnormalities (ARIA) in immunotherapy trials for Alzheimer’s disease: Need for prognostic biomarkers? J. Alzheimers Dis., 2016, 52(2), 417-420.
[http://dx.doi.org/10.3233/JAD-160122] [PMID: 27031492]
[49]
Lin, P.J.; Cohen, J.T.; Neumann, P.J. Preparing the health-care system to pay for new Alzheimer’s drugs. Alzheimers Dement., 2020, 16(11), 1568-1570.
[http://dx.doi.org/10.1002/alz.12155] [PMID: 32808733]
[50]
Hameed, S.; Fuh, J.L.; Senanarong, V.; Ebenezer, E.G.M.; Looi, I.; Dominguez, J.C.; Park, K.W.; Karanam, A.K.; Simon, O. Role of fluid biomarkers and PET imaging in early diagnosis and its clinical implication in the management of Alzheimer’s disease. J. Alzheimers Dis. Rep., 2020, 4(1), 21-37.
[http://dx.doi.org/10.3233/ADR-190143] [PMID: 32206755]
[51]
Nakamura, A.; Kaneko, N.; Villemagne, V.L.; Kato, T.; Doecke, J.; Doré, V.; Fowler, C.; Li, Q.X.; Martins, R.; Rowe, C.; Tomita, T.; Matsuzaki, K.; Ishii, K.; Ishii, K.; Arahata, Y.; Iwamoto, S.; Ito, K.; Tanaka, K.; Masters, C.L.; Yanagisawa, K. High performance plasma amyloid-β biomarkers for Alzheimer’s disease. Nature, 2018, 554(7691), 249-254.
[http://dx.doi.org/10.1038/nature25456] [PMID: 29420472]
[52]
Liu, K.Y.; Howard, R. Can we learn lessons from the FDA’s approval of aducanumab? Nat. Rev. Neurol., 2021, 17(11), 715-722.
[http://dx.doi.org/10.1038/s41582-021-00557-x] [PMID: 34535787]
[53]
Ferreira, S.T.; Lourenco, M.V.; Oliveira, M.M.; De Felice, F.G. Soluble amyloid-β oligomers as synaptotoxins leading to cognitive impairment in Alzheimer's disease. Front. Cell. Neurosci., 2015, 9, 191.
[http://dx.doi.org/10.3389/fncel.2015.00191] [PMID: 26074767]
[54]
Selkoe, D.J.; Hardy, J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol. Med., 2016, 8(6), 595-608.
[http://dx.doi.org/10.15252/emmm.201606210] [PMID: 27025652]
[55]
Rajasekhar, K.; Govindaraju, T. Current progress, challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer’s disease. RSC Advances, 2018, 8(42), 23780-23804.
[http://dx.doi.org/10.1039/C8RA03620A] [PMID: 35540246]
[56]
Dunstan, R.; Bussiere, T.; Fahrer, D.; Quigley, C.; Zhang, X.; Themeles, M.; Engber, T.; Rhodes, K.; Arastu, M.; Li, M. P4-005: Quantitation of beta-amyloid in transgenic mice using whole slide digital imaging and image analysis software. Alzheimers Dement., 2011, 7(4S_Part_20), S700.
[http://dx.doi.org/10.1016/j.jalz.2011.05.2024]
[57]
Reiss, A.B.; Arain, H.A.; Stecker, M.M.; Siegart, N.M.; Kasselman, L.J. Amyloid toxicity in Alzheimer’s disease. Rev. Neurosci., 2018, 29(6), 613-627.
[http://dx.doi.org/10.1515/revneuro-2017-0063] [PMID: 29447116]
[58]
Salazar, S.V.; Strittmatter, S.M. Cellular prion protein as a receptor for amyloid-β oligomers in Alzheimer’s disease. Biochem. Biophys. Res. Commun., 2017, 483(4), 1143-1147.
[http://dx.doi.org/10.1016/j.bbrc.2016.09.062] [PMID: 27639648]
[59]
Tian Hui Kwan, A.; Arfaie, S.; Therriault, J.; Rosa-Neto, P.; Gauthier, S. Lessons learnt from the second generation of anti-amyloid monoclonal antibodies clinical trials. Dement. Geriatr. Cogn. Disord., 2020, 49(4), 334-348.
[http://dx.doi.org/10.1159/000511506] [PMID: 33321511]
[60]
Hefti, F.; Goure, W.F.; Jerecic, J.; Iverson, K.S.; Walicke, P.A.; Krafft, G.A. The case for soluble Aβ oligomers as a drug target in Alzheimer’s disease. Trends Pharmacol. Sci., 2013, 34(5), 261-266.
[http://dx.doi.org/10.1016/j.tips.2013.03.002] [PMID: 23582316]
[61]
Cohen, S.I.A.; Linse, S.; Luheshi, L.M.; Hellstrand, E.; White, D.A.; Rajah, L.; Otzen, D.E.; Vendruscolo, M.; Dobson, C.M.; Knowles, T.P.J. Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism. Proc. Natl. Acad. Sci. USA, 2013, 110(24), 9758-9763.
[http://dx.doi.org/10.1073/pnas.1218402110] [PMID: 23703910]
[62]
Linse, S.; Scheidt, T.; Bernfur, K.; Vendruscolo, M.; Dobson, C.M.; Cohen, S.I.A.; Sileikis, E.; Lundqvist, M.; Qian, F.; O’Malley, T.; Bussiere, T.; Weinreb, P.H.; Xu, C.K.; Meisl, G.; Devenish, S.R.A.; Knowles, T.P.J.; Hansson, O. Kinetic fingerprints differentiate the mechanisms of action of anti-Aβ antibodies. Nat. Struct. Mol. Biol., 2020, 27(12), 1125-1133.
[http://dx.doi.org/10.1038/s41594-020-0505-6] [PMID: 32989305]
[63]
Dear, A.J.; Meisl, G.; Michaels, T.C.T.; Zimmermann, M.R.; Linse, S.; Knowles, T.P.J. The catalytic nature of protein aggregation. J. Chem. Phys., 2020, 152(4), 045101.
[http://dx.doi.org/10.1063/1.5133635] [PMID: 32007046]
[64]
Arosio, P.; Knowles, T.P.J.; Linse, S. On the lag phase in amyloid fibril formation. Phys. Chem. Chem. Phys., 2015, 17(12), 7606-7618.
[http://dx.doi.org/10.1039/C4CP05563B] [PMID: 25719972]
[65]
Avgerinos, K.I.; Ferrucci, L.; Kapogiannis, D. Effects of monoclonal antibodies against amyloid-β on clinical and biomarker outcomes and adverse event risks: A systematic review and meta-analysis of phase III RCTs in Alzheimer’s disease. Ageing Res. Rev., 2021, 68, 101339.
[http://dx.doi.org/10.1016/j.arr.2021.101339] [PMID: 33831607]
[66]
Cummings, J.; Aisen, P.; Lemere, C.; Atri, A.; Sabbagh, M.; Salloway, S. Aducanumab produced a clinically meaningful benefit in association with amyloid lowering. Alzheimers Res. Ther., 2021, 13(1), 98.
[http://dx.doi.org/10.1186/s13195-021-00838-z] [PMID: 33971962]
[67]
Howard, R.; Liu, K.Y. Questions EMERGE as Biogen claims aducanumab turnaround. Nat. Rev. Neurol., 2020, 16(2), 63-64.
[http://dx.doi.org/10.1038/s41582-019-0295-9] [PMID: 31784690]
[68]
Mo, J.J.; Li, J.; Yang, Z.; Liu, Z.; Feng, J.S. Efficacy and safety of anti-amyloid-β immunotherapy for Alzheimer’s disease: A systematic review and network meta-analysis. Ann. Clin. Transl. Neurol., 2017, 4(12), 931-942.
[http://dx.doi.org/10.1002/acn3.469] [PMID: 29296624]
[69]
Gamage, K.K.; Kumar, S. Aducanumab therapy ameliorates calcium overload in a mouse model of Alzheimer’s disease. J. Neurosci., 2017, 37(17), 4430-4432.
[http://dx.doi.org/10.1523/JNEUROSCI.0420-17.2017] [PMID: 28446659]
[70]
Kastanenka, K.V.; Bussiere, T.; Shakerdge, N.; Qian, F.; Weinreb, P.H.; Rhodes, K.; Bacskai, B.J. Immunotherapy with aducanumab restores calcium homeostasis in Tg2576 mice. J. Neurosci., 2016, 36(50), 12549-12558.
[http://dx.doi.org/10.1523/JNEUROSCI.2080-16.2016] [PMID: 27810931]
[71]
Kuller, L.H.; Lopez, O.L. ENGAGE and EMERGE: Truth and consequences? Alzheimers Dement., 2021, 17(4), 692-695.
[http://dx.doi.org/10.1002/alz.12286] [PMID: 33656288]
[72]
Study, the first real-world observational phase 4 study in Alzheimer’s disease at AAIC 2021. 2021. Available From: https://www.neurologylive.com/view/aducanumab-phase-4-real-world-observational-study-announced
[73]
Padda, I.S.; Parmar, M. Aducanumab; StatPearls Publishing.: Florida, 2022.
[74]
Knopman, D.S.; Jones, D.T.; Greicius, M.D. Failure to demonstrate efficacy of aducanumab: An analysis of the EMERGE and ENGAGE trials as reported by Biogen, December 2019. Alzheimers Dement., 2021, 17(4), 696-701.
[http://dx.doi.org/10.1002/alz.12213] [PMID: 33135381]

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