Login Register Cart 0
Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Anti-Amyloid-β Immunotherapy: A Leading Novel Avenue for Alzheimer's Disease

Author(s): Parth Sharma, Ritchu Babbar*, Twinkle Sharma, Piyush Madaan, Sandeep Arora and Vishnu Nayak Badavath

Volume 23, Issue 1, 2023

Published on: 22 August, 2022

Page: [53 - 66] Pages: 14

DOI: 10.2174/1389557522666220524090354

Price: $65

Abstract

Alzheimer’s disease or senile dementia is principally acknowledged by the gradual accumulation of neurotoxic amyloid- β protein in the brain and is considered as the initial event of the phenomenon of this asymptomatic ailment. It prompts the decline in cognitive performance, standard psychiatric functioning, and neuronal transmission across the brain. Significant inferences were withdrawn by utilizing the recently introduced disease-modifying anti- amyloid- β immunotherapy developed after performing the clinical and preclinical controlled trials to cure the neurodegenerative malady. This strategy is worthwhile because of the clinical relevance and specific targeted approach that exhibited the quenched immunotherapeutic effects and encouraged clinical findings. In vitro fabricated, anti- amyloid- β recombinant monoclonal antibodies are passively employed to promote clearance and antagonize the aggregation and synthesis of neurotoxic and degenerative aggregates of amyloid-β. Thus, passive immunotherapy has an adequate impact on treating this disorder, and currently, some other monoclonal pharmacological molecules are under clinical trials to defeat this severe exacerbation with more efficacy and clinical benefits. This review compendiously discusses the anti-amyloid-β immunotherapy, which will provide a more proficient framework to be employed as a potential therapeutic approach.

Keywords: Amyloid- β, cognitive impairment, dementia, immunotherapy, monoclonal antibody, neurodegeneration, tau protein.

« Previous Next »
Graphical Abstract

[1]
Finder, V.H. Alzheimer’s disease: A general introduction and pathomechanism. J. Alzheimers Dis., 2010, 22(Suppl. 3), 5-19.
[http://dx.doi.org/10.3233/JAD-2010-100975] [PMID: 20858960]
[2]
Panza, F.; Lozupone, M.; Logroscino, G.; Imbimbo, B.P. A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nat. Rev. Neurol., 2019, 15(2), 73-88.
[http://dx.doi.org/10.1038/s41582-018-0116-6] [PMID: 30610216]
[3]
Hebert, L.E.; Weuve, J.; Scherr, P.A.; Evans, D.A. Alzheimer disease in the United States (2010-2050) estimated using the 2010 census. Neurology, 2013, 80(19), 1778-1783.
[http://dx.doi.org/10.1212/WNL.0b013e31828726f5] [PMID: 23390181]
[4]
Gandy, S. The role of cerebral amyloid β accumulation in common forms of Alzheimer disease. J. Clin. Invest., 2005, 115(5), 1121-1129.
[http://dx.doi.org/10.1172/JCI25100] [PMID: 15864339]
[5]
Maggio, J.E.; Stimson, E.R.; Ghilardi, J.R.; Allen, C.J.; Dahl, C.E.; Whitcomb, D.C.; Vigna, S.R.; Vinters, H.V.; Labenski, M.E.; Mantyh, P.W. Reversible in vitro growth of Alzheimer disease beta-amyloid plaques by deposition of labeled amyloid peptide. Proc. Natl. Acad. Sci. USA, 1992, 89(12), 5462-5466.
[http://dx.doi.org/10.1073/pnas.89.12.5462] [PMID: 1608956]
[6]
Rijal Upadhaya, A.; Kosterin, I.; Kumar, S.; von Arnim, C.A.; Yamaguchi, H.; Fändrich, M.; Walter, J.; Thal, D.R. Biochemical stages of amyloid-β peptide aggregation and accumulation in the human brain and their association with symptomatic and pathologically preclinical Alzheimer’s disease. Brain, 2014, 137(Pt 3), 887-903.
[http://dx.doi.org/10.1093/brain/awt362] [PMID: 24519982]
[7]
Cheng, I.H.; Scearce-Levie, K.; Legleiter, J.; Palop, J.J.; Gerstein, H.; Bien-Ly, N.; Puoliväli, J.; Lesné, S.; Ashe, K.H.; Muchowski, P.J.; Mucke, L. Accelerating amyloid-β fibrillization reduces oligomer levels and functional deficits in Alzheimer disease mouse models. J. Biol. Chem., 2007, 282(33), 23818-23828.
[http://dx.doi.org/10.1074/jbc.M701078200] [PMID: 17548355]
[8]
Baig, M.H.; Ahmad, K.; Rabbani, G.; Choi, I. Use of peptides for the management of Alzheimer’s disease: Diagnosis and inhibition. Front. Aging Neurosci., 2018, 10, 21.
[http://dx.doi.org/10.3389/fnagi.2018.00021] [PMID: 29467644]
[9]
Salahuddin, P.; Rabbani, G.; Khan, R.H. The role of advanced glycation end products in various types of neurodegenerative disease: A therapeutic approach. Cell. Mol. Biol. Lett., 2014, 19(3), 407-437.
[http://dx.doi.org/10.2478/s11658-014-0205-5] [PMID: 25141979]
[10]
Baig, M.H.; Ahmad, K.; Rabbani, G.; Danishuddin, M.; Choi, I. Computer aided drug design and its application to the development of potential drugs for neurodegenerative disorders. Curr. Neuropharmacol., 2018, 16(6), 740-748.
[http://dx.doi.org/10.2174/1570159X15666171016163510] [PMID: 29046156]
[11]
Varshney, A.; Rabbani, G.; Badr, G.; Khan, R.H. Cosolvents induced unfolding and aggregation of keyhole limpet hemocyanin. Cell Biochem. Biophys., 2014, 69(1), 103-113.
[http://dx.doi.org/10.1007/s12013-013-9776-4] [PMID: 24242285]
[12]
Sen, P.; Ahmad, B.; Rabbani, G.; Khan, R.H. 2,2,2-Trifluroethanol induces simultaneous increase in α-helicity and aggregation in alkaline unfolded state of bovine serum albumin. Int. J. Biol. Macromol., 2010, 46(2), 250-254.
[http://dx.doi.org/10.1016/j.ijbiomac.2009.12.013] [PMID: 20060414]
[13]
Osborn, G.G.; Saunders, A.V. Current treatments for patients with Alzheimer disease. J. Osteopath. Med., 2010, 110(9)(Suppl. 8), S16-S26.
[http://dx.doi.org/10.7556/jaoa.2010.20042] [PMID: 20926739]
[14]
Olivares, D.; Deshpande, V.K.; Shi, Y.; Lahiri, D.K.; Greig, N.H.; Rogers, J.T.; Huang, X. N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for Alzheimer’s disease, vascular dementia and Parkinson’s disease. Curr. Alzheimer Res., 2012, 9(6), 746-758.
[http://dx.doi.org/10.2174/156720512801322564] [PMID: 21875407]
[15]
Yiannopoulou, K.G.; Papageorgiou, S.G. Current and future treatments in Alzheimer disease: An update. J. Cent. Nerv. Syst. Dis., 2020, 12, 1179573520907397.
[http://dx.doi.org/10.1177/1179573520907397] [PMID: 32165850]
[16]
Jindal, H.; Bhatt, B.; Sk, S.; Singh Malik, J. Alzheimer disease immunotherapeutics: Then and now. Hum. Vaccin. Immunother., 2014, 10(9), 2741-2743.
[http://dx.doi.org/10.4161/21645515.2014.970959] [PMID: 25483498]
[17]
Prins, N.D.; Scheltens, P. Treating Alzheimer’s disease with monoclonal antibodies: Current status and outlook for the future. Alzheimers Res. Ther., 2013, 5(6), 56.
[http://dx.doi.org/10.1186/alzrt220] [PMID: 24216217]
[18]
Brothers, H.M.; Gosztyla, M.L.; Robinson, S.R. The physiological roles of amyloid-β peptide hint at new ways to treat Alzheimer’s disease. Front. Aging Neurosci., 2018, 10, 118.
[http://dx.doi.org/10.3389/fnagi.2018.00118] [PMID: 29922148]
[19]
Alzheimer’s Association. 2017 Alzheimer’s disease facts and figures. Alzheimers Dement., 2017, 13(4), 325-373.
[http://dx.doi.org/10.1016/j.jalz.2017.02.001]
[20]
Murphy, M.P.; LeVine, H., III Alzheimer’s disease and the amyloid-β peptide. J. Alzheimers Dis., 2010, 19(1), 311-323.
[http://dx.doi.org/10.3233/JAD-2010-1221] [PMID: 20061647]
[21]
Masters, C.L.; Multhaup, G.; Simms, G.; Pottgiesser, J.; Martins, R.N.; Beyreuther, K. Neuronal origin of a cerebral amyloid: Neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J., 1985, 4(11), 2757-2763.
[http://dx.doi.org/10.1002/j.1460-2075.1985.tb04000.x] [PMID: 4065091]
[22]
Donohue, M.C.; Sperling, R.A.; Salmon, D.P.; Rentz, D.M.; Raman, R.; Thomas, R.G.; Weiner, M.; Aisen, P.S. The preclinical Alzheimer cognitive composite: Measuring amyloid-related decline. JAMA Neurol., 2014, 71(8), 961-970.
[http://dx.doi.org/10.1001/jamaneurol.2014.803] [PMID: 24886908]
[23]
Delrieu, J.; Ousset, P.J.; Voisin, T.; Vellas, B. Amyloid beta peptide immunotherapy in Alzheimer disease. Rev. Neurol. (Paris), 2014, 170(12), 739-748.
[http://dx.doi.org/10.1016/j.neurol.2014.10.003] [PMID: 25459121]
[24]
Panza, F.; Lozupone, M.; Seripa, D.; Imbimbo, B.P. Amyloid-β immunotherapy for alzheimer disease: Is it now a long shot? Ann. Neurol., 2019, 85(3), 303-315.
[http://dx.doi.org/10.1002/ana.25410] [PMID: 30635926]
[25]
Selkoe, D.J. Alzheimer’s disease: Genes, proteins, and therapy. Physiol. Rev., 2001, 81(2), 741-766.
[http://dx.doi.org/10.1152/physrev.2001.81.2.741] [PMID: 11274343]
[26]
Kimberly, W.T.; Zheng, J.B.; Guénette, S.Y.; Selkoe, D.J. The intracellular domain of the β-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J. Biol. Chem., 2001, 276(43), 40288-40292.
[http://dx.doi.org/10.1074/jbc.C100447200] [PMID: 11544248]
[27]
Gao, Y.; Pimplikar, S.W. The γ -secretase-cleaved C-terminal fragment of amyloid precursor protein mediates signaling to the nucleus. Proc. Natl. Acad. Sci. USA, 2001, 98(26), 14979-14984.
[http://dx.doi.org/10.1073/pnas.261463298] [PMID: 11742091]
[28]
Hyman, B.T. Amyloid-dependent and amyloid-independent stages of Alzheimer disease. Arch. Neurol., 2011, 68(8), 1062-1064.
[http://dx.doi.org/10.1001/archneurol.2011.70] [PMID: 21482918]
[29]
Arbel, M.; Solomon, B. Immunotherapy for Alzheimer’s disease: Attacking amyloid-β from the inside. Trends Immunol., 2007, 28(12), 511-513.
[http://dx.doi.org/10.1016/j.it.2007.09.005] [PMID: 17981084]
[30]
Van Uden, E.; Mallory, M.; Veinbergs, I.; Alford, M.; Rockenstein, E.; Masliah, E. Increased extracellular amyloid deposition and neuro-degeneration in human amyloid precursor protein transgenic mice deficient in receptor-associated protein. J. Neurosci., 2002, 22(21), 9298-9304.
[http://dx.doi.org/10.1523/JNEUROSCI.22-21-09298.2002] [PMID: 12417655]
[31]
Walsh, D.M.; Selkoe, D.J. Amyloid β-protein and beyond: The path forward in Alzheimer’s disease. Curr. Opin. Neurobiol., 2020, 61, 116-124.
[http://dx.doi.org/10.1016/j.conb.2020.02.003] [PMID: 32197217]
[32]
Karran, E.; Mercken, M.; De Strooper, B. The amyloid cascade hypothesis for Alzheimer’s disease: An appraisal for the development of therapeutics. Nat. Rev. Drug Discov., 2011, 10(9), 698-712.
[http://dx.doi.org/10.1038/nrd3505] [PMID: 21852788]
[33]
Donohue, M.C.; Sperling, R.A.; Petersen, R.; Sun, C.K.; Weiner, M.W.; Aisen, P.S. Alzheimer’s Disease Neuroimaging Initiative. Association between elevated brain amyloid and subsequent cognitive decline among cognitively normal persons. JAMA, 2017, 317(22), 2305-2316.
[http://dx.doi.org/10.1001/jama.2017.6669] [PMID: 28609533]
[34]
Wang, L.; Benzinger, T.L.; Su, Y.; Christensen, J.; Friedrichsen, K.; Aldea, P.; McConathy, J.; Cairns, N.J.; Fagan, A.M.; Morris, J.C.; Ances, B.M. Evaluation of tau imaging in staging Alzheimer disease and revealing interactions between β-amyloid and tauopathy. JAMA Neurol., 2016, 73(9), 1070-1077.
[http://dx.doi.org/10.1001/jamaneurol.2016.2078] [PMID: 27454922]
[35]
Castello, M.A.; Soriano, S. Rational heterodoxy: Cholesterol reformation of the amyloid doctrine. Ageing Res. Rev., 2013, 12(1), 282-288.
[http://dx.doi.org/10.1016/j.arr.2012.06.007] [PMID: 22771381]
[36]
Mucke, L.; Selkoe, D.J. Neurotoxicity of amyloid β-protein: Synaptic and network dysfunction. Cold Spring Harb. Perspect. Med., 2012, 2(7), 6338.
[http://dx.doi.org/10.1101/cshperspect.a006338]
[37]
Folch, J.; Ettcheto, M.; Petrov, D.; Abad, S.; Pedrós, I.; Marin, M.; Olloquequi, J.; Camins, A. Review of the advances in treatment for Alzheimer disease: Strategies for combating β-amyloid protein. Neurol., 2018, 33(1), 47-58.
[http://dx.doi.org/10.1016/j.nrleng.2015.03.019] [PMID: 25976937]
[38]
Drachman, D.A. The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimers Dement., 2014, 10(3), 372-380.
[http://dx.doi.org/10.1016/j.jalz.2013.11.003] [PMID: 24589433]
[39]
Cochran, J.N.; Hall, A.M.; Roberson, E.D. The dendritic hypothesis for Alzheimer’s disease pathophysiology. Brain Res. Bull., 2014, 103, 18-28.
[http://dx.doi.org/10.1016/j.brainresbull.2013.12.004] [PMID: 24333192]
[40]
Cohen, A.D.; Landau, S.M.; Snitz, B.E.; Klunk, W.E.; Blennow, K.; Zetterberg, H. Fluid and PET biomarkers for amyloid pathology in Alzheimer’s disease. Mol. Cell. Neurosci., 2019, 97, 3-17.
[http://dx.doi.org/10.1016/j.mcn.2018.12.004] [PMID: 30537535]
[41]
Liu, Y.H.; Giunta, B.; Zhou, H.D.; Tan, J.; Wang, Y.J. Immunotherapy for Alzheimer disease: The challenge of adverse effects. Nat. Rev. Neurol., 2012, 8(8), 465-469.
[http://dx.doi.org/10.1038/nrneurol.2012.118] [PMID: 22751529]
[42]
Panza, F.; Frisardi, V.; Solfrizzi, V.; Imbimbo, B.P.; Logroscino, G.; Santamato, A.; Greco, A.; Seripa, D.; Pilotto, A. Immunotherapy for Alzheimer’s disease: From anti-β-amyloid to tau-based immunization strategies. Immunotherapy, 2012, 4(2), 213-238.
[http://dx.doi.org/10.2217/imt.11.170] [PMID: 22339463]
[43]
Lemere, C.A.; Maier, M.; Jiang, L.; Peng, Y.; Seabrook, T.J. Amyloid-beta immunotherapy for the prevention and treatment of Alzheimer disease: Lessons from mice, monkeys, and humans. Rejuvenation Res., 2006, 9(1), 77-84.
[http://dx.doi.org/10.1089/rej.2006.9.77] [PMID: 16608400]
[44]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 2002, 297(5580), 353-356.
[http://dx.doi.org/10.1126/science.1072994] [PMID: 12130773]
[45]
Holmes, C.; Boche, D.; Wilkinson, D.; Yadegarfar, G.; Hopkins, V.; Bayer, A.; Jones, R.W.; Bullock, R.; Love, S.; Neal, J.W.; Zotova, E.; Nicoll, J.A. Long-term effects of Abeta42 immunisation in Alzheimer’s disease: Follow-up of a randomised, placebo-controlled phase I trial. Lancet, 2008, 372(9634), 216-223.
[http://dx.doi.org/10.1016/S0140-6736(08)61075-2] [PMID: 18640458]
[46]
Farlow, M.R.; Andreasen, N.; Riviere, M.E.; Vostiar, I.; Vitaliti, A.; Sovago, J.; Caputo, A.; Winblad, B.; Graf, A. Long-term treatment with active Aβ immunotherapy with CAD106 in mild Alzheimer’s disease. Alzheimers Res. Ther., 2015, 7(1), 23.
[http://dx.doi.org/10.1186/s13195-015-0108-3] [PMID: 25918556]
[47]
St-Amour, I.; Cicchetti, F.; Calon, F. Immunotherapies in Alzheimer’s disease: Too much, too little, too late or off-target? Acta Neuropathol., 2016, 131(4), 481-504.
[http://dx.doi.org/10.1007/s00401-015-1518-9] [PMID: 26689922]
[48]
Asuni, A.A.; Boutajangout, A.; Quartermain, D.; Sigurdsson, E.M. Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J. Neurosci., 2007, 27(34), 9115-9129.
[http://dx.doi.org/10.1523/JNEUROSCI.2361-07.2007] [PMID: 17715348]
[49]
Godyń, J.; Jończyk, J.; Panek, D.; Malawska, B. Therapeutic strategies for Alzheimer’s disease in clinical trials. Pharmacol. Rep., 2016, 68(1), 127-138.
[http://dx.doi.org/10.1016/j.pharep.2015.07.006] [PMID: 26721364]
[50]
Wang, Y.; Yan, T.; Lu, H.; Yin, W.; Lin, B.; Fan, W.; Zhang, X.; Fernandez-Funez, P. Lessons from anti-amyloid-β immunotherapies in Alzheimer disease: Aiming at a moving target. Neurodegener. Dis., 2017, 17(6), 242-250.
[http://dx.doi.org/10.1159/000478741] [PMID: 28787714]
[51]
Gilman, S.; Koller, M.; Black, R.S.; Jenkins, L.; Griffith, S.G.; Fox, N.C.; Eisner, L.; Kirby, L.; Rovira, M.B.; Forette, F.; Orgogozo, J.M. Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial. Neurology, 2005, 64(9), 1553-1562.
[http://dx.doi.org/10.1212/01.WNL.0000159740.16984.3C] [PMID: 15883316]
[52]
Rafii, M.S. Active immunotherapy for Alzheimer’s disease: The road ahead. J. Prev. Alzheimers Dis., 2015, 2(2), 78-79.
[http://dx.doi.org/10.14283/jpad.2015.59] [PMID: 28331846]
[53]
Levites, Y.; Das, P.; Price, R.W.; Rochette, M.J.; Kostura, L.A.; McGowan, E.M.; Murphy, M.P.; Golde, T.E. Anti-Abeta42- and anti-Abeta40-specific mAbs attenuate amyloid deposition in an Alzheimer disease mouse model. J. Clin. Invest., 2006, 116(1), 193-201.
[http://dx.doi.org/10.1172/JCI25410] [PMID: 16341263]
[54]
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]
[55]
Sengupta, U.; Nilson, A.N.; Kayed, R. The role of amyloid-β oligomers in toxicity, propagation, and immunotherapy. EBioMedicine, 2016, 6, 42-49.
[http://dx.doi.org/10.1016/j.ebiom.2016.03.035] [PMID: 27211547]
[56]
Bacskai, B.J.; Kajdasz, S.T.; Christie, R.H.; Carter, C.; Games, D.; Seubert, P.; Schenk, D.; Hyman, B.T. Imaging of amyloid-β deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy. Nat. Med., 2001, 7(3), 369-372.
[http://dx.doi.org/10.1038/85525] [PMID: 11231639]
[57]
Panza, F.; Solfrizzi, V.; Imbimbo, B.P.; Tortelli, R.; Santamato, A.; Logroscino, G. Amyloid-based immunotherapy for Alzheimer’s disease in the time of prevention trials: The way forward. Expert Rev. Clin. Immunol., 2014, 10(3), 405-419.
[http://dx.doi.org/10.1586/1744666X.2014.883921] [PMID: 24490853]
[58]
Panza, F.; Solfrizzi, V.; Imbimbo, B.P.; Logroscino, G. Amyloid-directed monoclonal antibodies for the treatment of Alzheimer’s disease: The point of no return? Expert Opin. Biol. Ther., 2014, 14(10), 1465-1476.
[http://dx.doi.org/10.1517/14712598.2014.935332] [PMID: 24981190]
[59]
Gardberg, A.S.; Dice, L.T.; Ou, S.; Rich, R.L.; Helmbrecht, E.; Ko, J.; Wetzel, R.; Myszka, D.G.; Patterson, P.H.; Dealwis, C. Molecular basis for passive immunotherapy of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2007, 104(40), 15659-15664.
[http://dx.doi.org/10.1073/pnas.0705888104] [PMID: 17895381]
[60]
Winblad, B.; Andreasen, N.; Minthon, L.; Floesser, A.; Imbert, G.; Dumortier, T.; Maguire, R.P.; Blennow, K.; Lundmark, J.; Staufenbiel, M.; Orgogozo, J.M.; Graf, A. Safety, tolerability, and antibody response of active Aβ immunotherapy with CAD106 in patients with Alzheimer’s disease: Randomised, double-blind, placebo-controlled, first-in-human study. Lancet Neurol., 2012, 11(7), 597-604.
[http://dx.doi.org/10.1016/S1474-4422(12)70140-0] [PMID: 22677258]
[61]
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]
[62]
Davtyan, H.; Ghochikyan, A.; Petrushina, I.; Hovakimyan, A.; Davtyan, A.; Poghosyan, A.; Marleau, A.M.; Movsesyan, N.; Kiyatkin, A.; Rasool, S.; Larsen, A.K.; Madsen, P.J.; Wegener, K.M.; Ditlevsen, D.K.; Cribbs, D.H.; Pedersen, L.O.; Agadjanyan, M.G. Immunogenicity, efficacy, safety, and mechanism of action of epitope vaccine (Lu AF20513) for Alzheimer’s disease: Prelude to a clinical trial. J. Neurosci., 2013, 33(11), 4923-4934.
[http://dx.doi.org/10.1523/JNEUROSCI.4672-12.2013] [PMID: 23486963]
[63]
Bouter, Y.; Noguerola, J.S.; Tucholla, P.; Crespi, G.A.; Parker, M.W.; Wiltfang, J.; Miles, L.A.; Bayer, T.A. Abeta targets of the biosimilar antibodies of Bapineuzumab, Crenezumab, Solanezumab in comparison to an antibody against N-truncated A beta in sporadic Alzheimer disease cases and mouse models. Acta Neuropathol., 2015, 130(5), 713-729.
[http://dx.doi.org/10.1007/s00401-015-1489-x]
[64]
Lemere, C.A.; Masliah, E. Can Alzheimer disease be prevented by amyloid-β immunotherapy? Nat. Rev. Neurol., 2010, 6(2), 108-119.
[http://dx.doi.org/10.1038/nrneurol.2009.219] [PMID: 20140000]
[65]
Roychaudhuri, R.; Yang, M.; Hoshi, M.M.; Teplow, D.B. Amyloid β-protein assembly and Alzheimer disease. J. Biol. Chem., 2009, 284(8), 4749-4753.
[http://dx.doi.org/10.1074/jbc.R800036200] [PMID: 18845536]
[66]
Dodel, R.; Balakrishnan, K.; Keyvani, K.; Deuster, O.; Neff, F.; Andrei-Selmer, L.C.; Röskam, S.; Stüer, C.; Al-Abed, Y.; Noelker, C.; Balzer-Geldsetzer, M.; Oertel, W.; Du, Y.; Bacher, M. Naturally occurring autoantibodies against β-amyloid: Investigating their role in transgenic animal and in vitro models of Alzheimer’s disease. J. Neurosci., 2011, 31(15), 5847-5854.
[http://dx.doi.org/10.1523/JNEUROSCI.4401-10.2011] [PMID: 21490226]
[67]
Relkin, N.R.; Szabo, P.; Adamiak, B.; Burgut, T.; Monthe, C.; Lent, R.W.; Younkin, S.; Younkin, L.; Schiff, R.; Weksler, M.E. 18-Month study of intravenous immunoglobulin for treatment of mild Alzheimer disease. Neurobiol. Aging, 2009, 30(11), 1728-1736.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.12.021] [PMID: 18294736]
[68]
Taguchi, H.; Planque, S.; Nishiyama, Y.; Szabo, P.; Weksler, M.E.; Friedland, R.P.; Paul, S. Catalytic antibodies to amyloid β peptide in defense against Alzheimer disease. Autoimmun. Rev., 2008, 7(5), 391-397.
[http://dx.doi.org/10.1016/j.autrev.2008.03.004] [PMID: 18486927]
[69]
Klyubin, I.; Betts, V.; Welzel, A.T.; Blennow, K.; Zetterberg, H.; Wallin, A.; Lemere, C.A.; Cullen, W.K.; Peng, Y.; Wisniewski, T.; Selkoe, D.J.; Anwyl, R.; Walsh, D.M.; Rowan, M.J. Amyloid β protein dimer-containing human CSF disrupts synaptic plasticity: Prevention by systemic passive immunization. J. Neurosci., 2008, 28(16), 4231-4237.
[http://dx.doi.org/10.1523/JNEUROSCI.5161-07.2008] [PMID: 18417702]
[70]
Spires-Jones, T.L.; Mielke, M.L.; Rozkalne, A.; Meyer-Luehmann, M.; de Calignon, A.; Bacskai, B.J.; Schenk, D.; Hyman, B.T. Passive immunotherapy rapidly increases structural plasticity in a mouse model of Alzheimer disease. Neurobiol. Dis., 2009, 33(2), 213-220.
[http://dx.doi.org/10.1016/j.nbd.2008.10.011] [PMID: 19028582]
[71]
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 Abeta oligomers that disrupt synaptic plasticity in vivo. Nat. Med., 2005, 11(5), 556-561.
[http://dx.doi.org/10.1038/nm1234] [PMID: 15834427]
[72]
Britschgi, M.; Olin, C.E.; Johns, H.T.; Takeda-Uchimura, Y.; LeMieux, M.C.; Rufibach, K.; Rajadas, J.; Zhang, H.; Tomooka, B.; Robinson, W.H.; Clark, C.M.; Fagan, A.M.; Galasko, D.R.; Holtzman, D.M.; Jutel, M.; Kaye, J.A.; Lemere, C.A.; Leszek, J.; Li, G.; Peskind, E.R.; Quinn, J.F.; Yesavage, J.A.; Ghiso, J.A.; Wyss-Coray, T. Neuroprotective natural antibodies to assemblies of amyloidogenic peptides decrease with normal aging and advancing Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2009, 106(29), 12145-12150.
[http://dx.doi.org/10.1073/pnas.0904866106] [PMID: 19581601]
[73]
Ostrowitzki, S.; Deptula, D.; Thurfjell, L.; Barkhof, F.; Bohrmann, B.; Brooks, D.J.; Klunk, W.E.; Ashford, E.; Yoo, K.; Xu, Z.X.; Loetscher, H.; Santarelli, L. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch. Neurol., 2012, 69(2), 198-207.
[http://dx.doi.org/10.1001/archneurol.2011.1538] [PMID: 21987394]
[74]
Selkoe, D.J. Alzheimer disease and aducanumab: Adjusting our approach. Nat. Rev. Neurol., 2019, 15(7), 365-366.
[http://dx.doi.org/10.1038/s41582-019-0205-1] [PMID: 31138932]
[75]
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]
[76]
Schneider, L. A resurrection of aducanumab for Alzheimer’s disease. Lancet Neurol., 2020, 19(2), 111-112.
[http://dx.doi.org/10.1016/S1474-4422(19)30480-6] [PMID: 31978357]
[77]
Nisticò, R.; Borg, J.J. Aducanumab for Alzheimer’s disease: A regulatory perspective. Pharmacol. Res., 2021, 171, 105754.
[http://dx.doi.org/10.1016/j.phrs.2021.105754] [PMID: 34217830]
[78]
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]
[79]
Leinenga, G.; Koh, W.K.; Götz, J. A comparative study of the effects of Aducanumab and scanning ultrasound on amyloid plaques and behavior in the APP23 mouse model of Alzheimer disease. Alzheimers Res. Ther., 2021, 13(1), 76.
[http://dx.doi.org/10.1186/s13195-021-00809-4] [PMID: 33836798]
[80]
Yang, P.; Sun, F. Aducanumab: The first targeted Alzheimer’s therapy. Drug Discov. Ther., 2021, 15(3), 166-168.
[http://dx.doi.org/10.5582/ddt.2021.01061] [PMID: 34234067]
[81]
Retinasamy, T.; Shaikh, M.F. Aducanumab for Alzheimer’s disease: An update. Neurosci. Res. Notes, 2021, 4(2), 17-20.
[http://dx.doi.org/10.31117/neuroscirn.v4i2.81]
[82]
Pul, R.; Dodel, R.; Stangel, M. Antibody-based therapy in Alzheimer’s disease. Expert Opin. Biol. Ther., 2011, 11(3), 343-357.
[http://dx.doi.org/10.1517/14712598.2011.552884] [PMID: 21261567]
[83]
Siemers, E.R.; Sundell, K.L.; Carlson, C.; Case, M.; Sethuraman, G.; Liu-Seifert, H.; Dowsett, S.A.; Pontecorvo, M.J.; Dean, R.A.; Demattos, R. Phase 3 solanezumab trials: Secondary outcomes in mild Alzheimer’s disease patients. Alzheimers Dement., 2016, 12(2), 110-120.
[http://dx.doi.org/10.1016/j.jalz.2015.06.1893] [PMID: 26238576]
[84]
Samadi, H.; Sultzer, D. Solanezumab for Alzheimer’s disease. Expert Opin. Biol. Ther., 2011, 11(6), 787-798.
[http://dx.doi.org/10.1517/14712598.2011.578573] [PMID: 21504387]
[85]
Madrasi, K.; Das, R.; Mohmmadabdul, H.; Lin, L.; Hyman, B.T.; Lauffenburger, D.A.; Albers, M.W.; Rissman, R.A.; Burke, J.M.; Apgar, J.F.; Wille, L.; Gruenbaum, L.; Hua, F. Systematic in silico analysis of clinically tested drugs for reducing amyloid-beta plaque accumulation in Alzheimer’s disease. Alzheimers Dement., 2021, 17(9), 1487-1498.
[http://dx.doi.org/10.1002/alz.12312] [PMID: 33938131]
[86]
Imbimbo, B.P.; Ottonello, S.; Frisardi, V.; Solfrizzi, V.; Greco, A.; Seripa, D.; Pilotto, A.; Panza, F. Solanezumab for the treatment of mild-to-moderate Alzheimer’s disease. Expert Rev. Clin. Immunol., 2012, 8(2), 135-149.
[http://dx.doi.org/10.1586/eci.11.93] [PMID: 22288451]
[87]
Tayeb, H.O.; Murray, E.D.; Price, B.H.; Tarazi, F.I. Bapineuzumab and solanezumab for Alzheimer’s disease: Is the ‘amyloid cascade hypothesis’ still alive? Expert Opin. Biol. Ther., 2013, 13(7), 1075-1084.
[http://dx.doi.org/10.1517/14712598.2013.789856] [PMID: 23574434]
[88]
Kerchner, G.A.; Boxer, A.L. Bapineuzumab. Expert Opin. Biol. Ther., 2010, 10(7), 1121-1130.
[http://dx.doi.org/10.1517/14712598.2010.493872] [PMID: 20497044]
[89]
Salloway, S.; Sperling, R.; Gilman, S.; Fox, N.C.; Blennow, K.; Raskind, M.; Sabbagh, M.; Honig, L.S.; Doody, R.; van Dyck, C.H.; Mulnard, R.; Barakos, J.; Gregg, K.M.; Liu, E.; Lieberburg, I.; Schenk, D.; Black, R.; Grundman, M. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology, 2009, 73(24), 2061-2070.
[http://dx.doi.org/10.1212/WNL.0b013e3181c67808] [PMID: 19923550]
[90]
Wilcock, G.K. Bapineuzumab in Alzheimer’s disease: Where now? Lancet Neurol., 2010, 9(2), 134-136.
[http://dx.doi.org/10.1016/S1474-4422(09)70359-X] [PMID: 20129159]
[91]
Panza, F.; Frisardi, V.; Imbimbo, B.P.; D’Onofrio, G.; Pietrarossa, G.; Seripa, D.; Pilotto, A.; Solfrizzi, V. Bapineuzumab: Anti-β-amyloid monoclonal antibodies for the treatment of Alzheimer’s disease. Immunotherapy, 2010, 2(6), 767-782.
[http://dx.doi.org/10.2217/imt.10.80] [PMID: 21091109]
[92]
Black, R.S.; Sperling, R.A.; Safirstein, B.; Motter, R.N.; Pallay, A.; Nichols, A.; Grundman, M. A single ascending dose study of bapineuzumab in patients with Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2010, 24(2), 198-203.
[http://dx.doi.org/10.1097/WAD.0b013e3181c53b00] [PMID: 20505438]
[93]
Novakovic, D.; Feligioni, M.; Scaccianoce, S.; Caruso, A.; Piccinin, S.; Schepisi, C.; Errico, F.; Mercuri, N.B.; Nicoletti, F.; Nisticò, R. Profile of gantenerumab and its potential in the treatment of Alzheimer’s disease. Drug Des. Devel. Ther., 2013, 7, 1359-1364.
[http://dx.doi.org/10.2147/DDDT.S53401] [PMID: 24255592]
[94]
Salloway, S.; Farlow, M.; McDade, E.; Clifford, D.B.; Wang, G.; Llibre-Guerra, J.J.; Hitchcock, J.M.; Mills, S.L.; Santacruz, A.M.; Aschen-brenner, A.J.; Hassenstab, J.; Benzinger, T.L.S.; Gordon, B.A.; Fagan, A.M.; Coalier, K.A.; Cruchaga, C.; Goate, A.A.; Perrin, R.J.; Xiong, C.; Li, Y.; Morris, J.C.; Snider, B.J.; Mummery, C.; Surti, G.M.; Hannequin, D.; Wallon, D.; Berman, S.B.; Lah, J.J.; Jimenez-Velazquez, I.Z.; Roberson, E.D.; van Dyck, C.H.; Honig, L.S.; Sánchez-Valle, R.; Brooks, W.S.; Gauthier, S.; Galasko, D.R.; Masters, C.L.; Brosch, J.R.; Hsiung, G.R.; Jayadev, S.; Formaglio, M.; Masellis, M.; Clarnette, R.; Pariente, J.; Dubois, B.; Pasquier, F.; Jack, C.R., Jr; Koeppe, R.; Snyder, P.J.; Aisen, P.S.; Thomas, R.G.; Berry, S.M.; Wendelberger, B.A.; Andersen, S.W.; Holdridge, K.C.; Mintun, M.A.; Yaari, R.; Sims, J.R.; Baudler, M.; Delmar, P.; Doody, R.S.; Fontoura, P.; Giacobino, C.; Kerchner, G.A.; Bateman, R.J.; Formaglio, M.; Mills, S.L.; Pariente, J.; van Dyck, C.H. A trial of gantenerumab or solanezumab in dominantly inherited Alzheimer’s disease. Nat. Med., 2021, 27(7), 1187-1196.
[http://dx.doi.org/10.1038/s41591-021-01369-8] [PMID: 34155411]
[95]
Al Ojaimi, Y.; Blin, T.; Lamamy, J.; Gracia, M.; Pitiot, A.; Denevault-Sabourin, C.; Joubert, N.; Pouget, J.P.; Gouilleux-Gruart, V.; Heuze-Vourc’h, N.; Lanznaster, D.; Poty, S.; Secher, T. Therapeutic antibodies- natural and pathological barriers and strategies to overcome them. Pharmacol. Ther., 2021, 233, 108022.
[http://dx.doi.org/10.1016/j.pharmthera.2021.108022]
[96]
Delrieu, J.; Ousset, P.J.; Vellas, B. Gantenerumab for the treatment of Alzheimer’s disease. Expert Opin. Biol. Ther., 2012, 12(8), 1077-1086.
[http://dx.doi.org/10.1517/14712598.2012.688022] [PMID: 22583155]
[97]
Panza, F.; Solfrizzi, V.; Imbimbo, B.P.; Giannini, M.; Santamato, A.; Seripa, D.; Logroscino, G. Efficacy and safety studies of gantenerumab in patients with Alzheimer’s disease. Expert Rev. Neurother., 2014, 14(9), 973-986.
[http://dx.doi.org/10.1586/14737175.2014.945522] [PMID: 25081412]
[98]
Salloway, S.; Honigberg, L.A.; Cho, W.; Ward, M.; Friesenhahn, M.; Brunstein, F.; Quartino, A.; Clayton, D.; Mortensen, D.; Bittner, T.; Ho, C.; Rabe, C.; Schauer, S.P.; Wildsmith, K.R.; Fuji, R.N.; Suliman, S.; Reiman, E.M.; Chen, K.; Paul, R. Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer’s disease (BLAZE). Alzheimers Res. Ther., 2018, 10(1), 96.
[http://dx.doi.org/10.1186/s13195-018-0424-5] [PMID: 30231896]
[99]
Cummings, J.L.; Cohen, S.; van Dyck, C.H.; Brody, M.; Curtis, C.; Cho, W.; Ward, M.; Friesenhahn, M.; Rabe, C.; Brunstein, F.; Quartino, A.; Honigberg, L.A.; Fuji, R.N.; Clayton, D.; Mortensen, D.; Ho, C.; Paul, R. ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease. Neurology, 2018, 90(21), e1889-e1897.
[http://dx.doi.org/10.1212/WNL.0000000000005550] [PMID: 29695589]
[100]
Yoshida, K.; Moein, A.; Bittner, T.; Ostrowitzki, S.; Lin, H.; Honigberg, L.; Jin, J.Y.; Quartino, A. Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer’s disease. Alzheimers Res. Ther., 2020, 12(1), 16.
[http://dx.doi.org/10.1186/s13195-020-0580-2] [PMID: 31969177]
[101]
Tariot, P.N.; Lopera, F.; Langbaum, J.B.; Thomas, R.G.; Hendrix, S.; Schneider, L.S.; Rios-Romenets, S.; Giraldo, M.; Acosta, N.; Tobon, C.; Ramos, C.; Espinosa, A.; Cho, W.; Ward, M.; Clayton, D.; Friesenhahn, M.; Mackey, H.; Honigberg, L.; Sanabria Bohorquez, S.; Chen, K.; Walsh, T.; Langlois, C.; Reiman, E.M. The Alzheimer’s prevention initiative autosomal-dominant Alzheimer’s disease trial: A study of crenezumab versus placebo in preclinical PSEN1 E280A mutation carriers to evaluate efficacy and safety in the treatment of autosomal-dominant Alzheimer’s disease, including a placebo-treated noncarrier cohort. Alzheimers Dement. (N. Y.), 2018, 4(1), 150-160.
[http://dx.doi.org/10.1016/j.trci.2018.02.002] [PMID: 29955659]
[102]
Meilandt, W.J.; Maloney, J.A.; Imperio, J.; Lalehzadeh, G.; Earr, T.; Crowell, S.; Bainbridge, T.W.; Lu, Y.; Ernst, J.A.; Fuji, R.N.; Atwal, J.K. Characterization of the selective in vitro and in vivo binding properties of crenezumab to oligomeric Aβ. Alzheimers Res. Ther., 2019, 11(1), 97.
[http://dx.doi.org/10.1186/s13195-019-0553-5] [PMID: 31787113]
[103]
Guthrie, H.; Honig, L.S.; Lin, H.; Sink, K.M.; Blondeau, K.; Quartino, A.; Dolton, M.; Carrasco-Triguero, M.; Lian, Q.; Bittner, T.; Clayton, D.; Smith, J.; Ostrowitzki, S. Safety, tolerability and pharmacokinetics of crenezumab in patients with mild to moderate Alzheimer’s Disease treated with escalating doses for upto 133 weeks. J. Alzheimers Dis., 2020, 76(3), 967-979.
[http://dx.doi.org/10.3233/JAD-200134]
[104]
Lowe, S.L.; Willis, B.A.; Hawdon, A.; Natanegara, F.; Chua, L.; Foster, J.; Shcherbinin, S.; Ardayfio, P.; Sims, J.R. Donanemab (LY3002813) dose-escalation study in Alzheimer’s disease. Alzheimers Dement. (N. Y.), 2021, 7(1), e12112.
[http://dx.doi.org/10.1002/trc2.12112] [PMID: 33614890]
[105]
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]
[106]
Doggrell, S.A. Still grasping at straws: Donanemab in Alzheimer’s disease. Expert Opin. Investig. Drugs, 2021, 30(8), 797-801.
[http://dx.doi.org/10.1080/13543784.2021.1948010] [PMID: 34162295]
[107]
Ayton, S. Brain volume loss due to donanemab. Eur. J. Neurol., 2021, 28(9), e67-e68.
[http://dx.doi.org/10.1111/ene.15007] [PMID: 34224184]
[108]
Bullain, S.; Doody, R. What works and what does not work in Alzheimer’s disease? From interventions on risk factors to anti-amyloid trials. J. Neurochem., 2020, 155(2), 120-136.
[http://dx.doi.org/10.1111/jnc.15023] [PMID: 32277473]

Rights & Permissions Print Cite
Article Metrics
3
© 2024 Bentham Science Publishers | Privacy Policy