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Amyloid-directed monoclonal antibodies for the treatment of Alzheimer’s disease: the point of no return?

, MD PhD, , MD PhD, , PhD & , MD PhD

Bibliography

  • Schneider LS, Mangialasche F, Andreasen N, et al. Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014. J Intern Med 2014;275:251-83
  • Panza F, Logroscino G, Imbimbo BP, Solfrizzi V. Is there still any hope for amyloid-based immunotherapy for Alzheimer’s disease? Curr Opin Psychiatry 2014;27:128-37
  • Walter J, Kaether C, Steiner H, Haass C. The cell biology of Alzheimer’s disease: uncovering the secrets of secretases. Curr Opin Neurobiol 2001;11:585-90
  • Dubois B, Feldman HH, Jacova C, et al. Research criteria for the diagnosis of Alzheimer’s disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;6:734-46
  • Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:280-92
  • Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011;7:270-9
  • Sperling RA, Karlawish J, Johnson KA. Preclinical Alzheimer disease-the challenges ahead. Nat Rev Neurol 2013;9:54-8
  • Bateman RJ, Xiong C, Benzinger TL, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med 2012;367:795-804
  • Villemagne VL, Burnham S, Bourgeat P, et al. Australian Imaging Biomarkers and Lifestyle (AIBL) Research Group. Amyloid beta deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: a prospective cohort study. Lancet Neurol 2013;12:357-67
  • Desikan RS, McEvoy LK, Thompson WK, et al. Amyloid-beta-associated clinical decline occurs only in the presence of elevated Ptau. Arch Neurol 2012;69:709-13
  • Knopman DS, Jack CR Jr, Wiste HJ, et al. Short-term clinical outcomes for stages of NIA–AA preclinical Alzheimer disease. Neurology 2012;78:1576-82
  • Jack CR Jr, Knopman DS, Weigand SD, et al. An operational approach to NIA–AA criteria for preclinical Alzheimer’s disease. Ann Neurol 2012;71:765-75
  • Knopman DS, Jack CR Jr, Wiste HJ, et al. Brain injury biomarkers are not dependent on beta-amyloid in normal elderly. Ann Neurol 2013;73:472-80
  • Frisardi V, Solfrizzi V, Imbimbo BP, et al. Towards disease-modifying treatment of Alzheimer’s disease: drugs targeting beta-amyloid. Curr Alzheimer Res 2010;7:40-55
  • Lambracht-Washington D, Rosenberg RN. Advances in the development of vaccines for Alzheimer’s disease. Discov Med 2013;15:319-26
  • Lemere CA. Immunotherapy for Alzheimer’s disease: hoops and hurdles. Mol Neurodegener 2013;8:36
  • Bard F, Cannon C, Barbour R, et al. Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 2000;6:916-19
  • Morgan D. Mechanisms of A beta plaque clearance following passive A beta immunization. Neurodegener Dis 2005;2:261-6
  • Panza F, Frisardi V, Imbimbo BP, et al. Anti-β-amyloid immunotherapy for Alzheimer’s disease: focus on bapineuzumab. Curr Alzheimer Res 2011;8:808-17
  • Imbimbo BP, Ottonello S, Frisardi V, et al. Solanezumab for the treatment of mild-to-moderate Alzheimer’s disease. Expert Rev Clin Immunol 2012;8:135-49
  • Tayeb HO, Murray ED, Price BH, Tarazi FI. Bapineuzumab and solanezumab for Alzheimer’s disease: is the ’amyloid cascade hypothesis’ still alive? Expert Opin Biol Ther 2013;13:1075-84
  • Salloway S, Sperling R, Fox NC, et al. Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer’s disease. N Engl J Med 2014;370:322-33
  • Doody RS, Thomas RG, Farlow M, et al. Phase 3 trials of solanezumab for mild-to-moderate Alzheimer’s disease. N Engl J Med 2014;370:311-21
  • Rinne JO, Brooks DJ, Rossor MN, et al. 11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer’s disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Lancet Neurol 2010;9:363-72
  • Blennow K, Zetterberg H, Rinne JO, et al. AAB-001 201/202 Investigators. Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease. Arch Neurol 2012;69:1002-10
  • Sperling RA, Jack CR Jr, Black SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer’s Association Research Roundtable Workgroup. Alzheimers Dement 2011;7:367-85
  • Salloway S, Sperling R, Gilman S, et al. A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease. Neurology 2009;73:2061-70
  • Karran E, Hardy J. Antiamyloid therapy for Alzheimer’s disease–are we on the right road? N Engl J Med 2014;370:377-8
  • Maia LF, Kaeser SA, Reichwald J, et al. Changes in amyloid-β and Tau in the cerebrospinal fluid of transgenic mice overexpressing amyloid precursor protein. Sci Transl Med 2013;5:194re2
  • Fagan AM, Xiong C, Jasielec MS, et al. Dominantly Inherited Alzheimer Network. Longitudinal change in CSF biomarkers in autosomal-dominant Alzheimer’s disease. Sci Transl Med 2014;6:226ra30
  • Pfizer and JANSSEN Alzheimer Immunotherapy Research & Development, LLC. Study Evaluating The Safety Of AAB-003 (PF-05236812) In Subjects With Alzheimer’s Disease. ClinicalTrials.gov NCT01193608. Available from: http://clinicaltrials.gov/ct2/show/NCT01193608?term=NCT01193608&rank=1 [Accessed 20 May 2014]
  • Pfizer and JANSSEN Alzheimer Immunotherapy Research & Development, LLC. Open Label Extension Study Evaluating Safety and Tolerability of AAB-003 (PF-05236812) in Subject With Mild to Moderate Alzheimer’s Disease. ClinicalTrials.gov NCT01369225. Available from: http://clinicaltrials.gov/ct2/show/NCT01369225?term=NCT01369225&rank=1 [Accessed 20 May 2014]
  • Siemers ER, Friedrich S, Dean RA, et al. Safety and changes in plasma and cerebrospinal fluid amyloid-beta after a single administration of an amyloid-beta monoclonal antibody in subjects with Alzheimer disease. Clin Neuropharmacol 2010;33:67-73
  • Farlow M, Arnold SE, van Dyck CH, et al. Safety and biomarker effects of solanezumab in patients with Alzheimer’s disease. Alzheimers Dement 2012;8:261-71
  • Eli Lilly and Co. Continued Safety Monitoring of Solanezumab in Alzheimer’s Disease (EXPEDITION EXT). ClinicalTrials.gov NCT01127633. Available from: http://clinicaltrials.gov/ct2/show/NCT01127633?term=NCT00905372&rank=2 [Accessed 20 May 2014]
  • Eli Lilly and Co. Progress of Mild Alzheimer’s Disease in Participants on Solanezumab Versus Placebo (EXPEDITION3). ClinicalTrials.gov NCT01900665. Available from: http://clinicaltrials.gov/ct2/show/NCT01900665?term=NCT01900665&rank=1 [Accessed 20 May 2014]
  • Moreth J, Mavoungou C, Schindowski K. Passive anti-amyloid immunotherapy in Alzheimer’s disease: what are the most promising targets? Immun Ageing 2013;10:18
  • Panza F, Solfrizzi V, Imbimbo BP, et al. Amyloid-based immunotherapy for Alzheimer’s disease in the time of prevention trials: the way forward. Expert Rev Clin Immunol 2014;10:405-19
  • Coric V, van Dyck CH, Salloway S, et al. Safety and tolerability of the γ-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol 2012;69:1430-40
  • Doody RS, Raman R, Siemers E, et al. A phase 2 trial of semagacestat for treatment of Alzheimer’s disease. N Engl J Med 2013;369:341-50
  • Sperling RA, Rentz DM, Johnson KA, et al. The A4 Study: stopping AD before symptoms begin? Sci Transl Med 2014;6:228fs13
  • Mills SM, Mallmann J, Santacruz AM, et al. Preclinical trials in autosomal dominant AD: implementation of the DIAN-TU trial. Rev Neurol (Paris) 2013;169:737-43
  • Reiman EM, Langbaum JB, Fleisher AS, et al. Alzheimer’s Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. J Alzheimers Dis 2011;26(Suppl 3):321-9
  • Sperling RA, Jack CR Jr, Aisen PS. Testing the right target and right drug at the right stage. Sci Transl Med 2011;3:111cm33
  • Solomon A, Mangialasche F, Richard E, et al. Advances in the prevention of Alzheimer’s disease and dementia. J Intern Med 2014;275:229-50
  • Eli Lilly and Co. with Alzheimer’s Disease Cooperative Study (ADCS). Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss (A4). ClinicalTrials.gov NCT02008357. Available from: http://clinicaltrials.gov/ct2/show/NCT02008357?term=Anti-Amyloid+Treatment+in+Asymptomatic+AD&rank=1 [Accessed 20 May 2014]
  • Moulder KL, Snider BJ, Mills SL, et al. Dominantly Inherited Alzheimer Network: facilitating research and clinical trials. Alzheimers Res Ther 2013;5:48
  • Washington University School of Medicine with Eli Lilly and Co., Hoffmann-La Roche, Alzheimer’s Association, National Institute on Aging (NIA), and Avid Radiopharmaceuticals. Dominantly Inherited Alzheimer Network Trial: An Opportunity to Prevent Dementia. A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset Alzheimer’s Disease Caused by a Genetic Mutation. (DIAN TU). ClinicalTrials.gov NCT01760005. Available from: http://clinicaltrials.gov/ct2/show/NCT01760005?term=NCT01760005&rank=1 [Accessed 20 May 2014]
  • Bohrmann B, Baumann K, Benz J, et al. Gantenerumab: a novel human anti-Aβ antibody demonstrates sustained cerebral amyloid-β binding and elicits cell-mediated removal of human amyloid-beta. J Alzheimers Dis 2012;28:49-69
  • Delrieu J, Ousset PJ, Vellas B. Gantenerumab for the treatment of Alzheimer’s disease. Expert Opin Biol Ther 2012;12:1077-86
  • Ostrowitzki S, Deptula D, Thurfjell L, et al. Mechanism of amyloid removal in patients with Alzheimer disease treated with gantenerumab. Arch Neurol 2012;69:198-207
  • Hoffmann-La Roche. A Study of Gantenerumab in Patients With Prodromal Alzheimer’s Disease. ClinicalTrials.gov NCT01224106. Available from: http://clinicaltrials.gov/ct2/show/NCT01224106?term=NCT01224106&rank=1 [Accessed 20 May 2014]
  • Genentech and Banner Alzheimer’s Institute. A Study of Crenezumab Versus Placebo in Preclinical PSEN1 E280A Mutation Carriers to Evaluate Efficacy and Safety in the Treatment of Autosomal-Dominant Alzheimer Disease, Including a Placebo-Treated Noncarrier Cohort. ClinicalTrials.gov NCT01998841. Available from: http://clinicaltrials.gov/ct2/show/NCT01224106?term=NCT01224106&rank=1 [Accessed 20 May 2014]
  • Lemere CA, Lopera F, Kosik KS, et al. The E280A presenilin 1 Alzheimer mutation produces increased Aβ42 deposition and severe cerebellar pathology. Nat Med 1996;2:1146-50
  • Lopera F, Ardilla A, Martinez A, et al. Clinical features of early-onset Alzheimer disease in a large kindred with an E280A presenilin-1 mutation. JAMA 1997;277:793-9
  • Adolfsson O, Pihlgren M, Toni N, et al. An effector-reduced anti-beta-amyloid (Aβ) antibody with unique Aβ binding properties promotes neuroprotection and glial engulfment of Abeta. J Neurosci 2012;32:9677-89
  • Genentech. A Long-Term Safety Extension Study of Studies ABE4869g And ABE4955g in Patients With Mild To Moderate Alzheimer’s Disease Treated With Crenezumab. ClinicalTrials.gov NCT01723826. Available from: http://clinicaltrials.gov/ct2/show/NCT01723826?term=NCT01723826&rank=1 [Accessed 20 May 2014]
  • Caselli RJ, Reiman EM. Characterizing the preclinical stages of Alzheimer’s disease and the prospect of presymptomatic intervention. J Alzheimers Dis 2013;33(Suppl 1):S405-16
  • Kozauer N, Katz R. Regulatory innovation and drug development for early-stage Alzheimer’s disease. N Engl J Med 2013;368:1169-71
  • Lesné S, Koh MT, et al. A specific amyloid-β protein assembly in the brain impairs memory. Nature 2006;440:352-7
  • Koffie RM, Meyer-Luehmann M, Hashimoto T, et al. Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci USA 2009;106:4012-17
  • Lee EB, Leng LZ, Zhang B, et al. Targeting amyloid-β peptide (Aβ) oligomers by passive immunization with a conformation-selective monoclonal antibody improves learning and memory in Abeta precursor protein (APP) transgenic mice. J Biol Chem 2006;281:4292-9
  • Lambert MP, Velasco PT, Chang L, et al. Monoclonal antibodies that target pathological assemblies of Abeta. J Neurochem 2007;100:23-35
  • Frost JL, Liu B, Kleinschmidt M, et al. Passive immunization against pyroglutamate-3 amyloid-beta reduces plaque burden in Alzheimer’s-like transgenic mice: a pilot study. Neurodegenerative Dis 2012;10:265-70
  • Kim J, Eltorai AE, Jiang H, et al. Anti-apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of Abeta amyloidosis. J Exp Med 2012;209:2149-56
  • DeMattos RB, Lu J, Tang Y, et al. A plaque-specific antibody clears existing β-amyloid plaques in Alzheimer’s disease mice. Neuron 2012;76:908-20
  • Morales-Corraliza J, Schmidt SD, Mazzella MJ, et al. Immunization targeting a minor plaque constituent clears β-amyloid and rescues behavioral deficits in an Alzheimer’s disease mouse model. Neurobiol Aging 2013;34:137-45
  • Weller RO, Subash M, Preston SD, et al. Perivascular drainage of amyloid-beta peptides from the brain and its failure in cerebral amyloid angiopathy and Alzheimer’s disease. Brain Pathol 2008;18:253-66
  • Hawkes CA, Härtig W, Kacza J, et al. Perivascular drainage of solutes is impaired in the ageing mouse brain and in the presence of cerebral amyloid angiopathy. Acta Neuropathol 2011;121:431-43
  • Carare RO, Hawkes CA, Jeffrey M, et al. Review: cerebral amyloid angiopathy, prion angiopathy, CADASIL and the spectrum of protein elimination failure angiopathies (PEFA) in neurodegenerative disease with a focus on therapy. Neuropathol Appl Neurobiol 2013;39:593-611
  • Boche D, Zotova E, Weller RO, et al. Consequence of Abeta immunization on the vasculature of human Alzheimer’s disease brain. Brain 2008;131:3299-310
  • Wilcock DM, Rojiani A, Rosenthal A, et al. Passive immunotherapy against Abeta in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage. J Neuroinflammation 2004;1:24
  • Prada CM, Garcia-Alloza M, Betensky RA, et al. Antibody-mediated clearance of amyloid-beta peptide from cerebral amyloid angiopathy revealed by quantitative in vivo imaging. J Neurosci 2007;27:1973-80
  • Iqbal K, Liu F, Gong CX, et al. Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 2009;118:53-69
  • Panza F, Frisardi V, Solfrizzi V, et al. Immunotherapy for Alzheimer’s disease: from anti-β-amyloid to tau-based immunization strategies. Immunotherapy 2012;4:213-38
  • Krstic D, Knuesel I. Deciphering the mechanism underlying late-onset Alzheimer disease. Nat Rev Neurol 2012;9:25-34
  • Lee HP, Zhu X, Casadesus G, et al. Antioxidant approaches for the treatment of Alzheimer’s disease. Expert Rev Neurother 2010;10:1201-8
  • de la Torre JC. Vascular risk factors: a ticking time bomb to Alzheimer’s disease. Am J Alzheimers Dis Other Demen 2013;28:551-9
  • Wang YJ. Alzheimer disease: lessons from immunotherapy for Alzheimer disease. Nat Rev Neurol 2014;10:188-9
  • Deng J, Hou H, Giunta B, et al. Autoreactive-Aβ antibodies promote APP beta-secretase processing. J Neurochem 2012;120:732-40
  • Liu YH, Giunta B, Zhou HD, et al. Immunotherapy for Alzheimer disease: the challenge of adverse effects. Nat Rev Neurol 2012;8:465-9

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