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Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer's Disease
by
Osswald, Gunilla
, Eriksson, Fredrik
, Möller, Christer
, Johannesson, Malin
, Nygren, Patrik
, Laudon, Hanna
, Söderberg, Linda
, Lannfelt, Lars
in
Aducanumab
/ Aggregates
/ Alzheimer Disease - drug therapy
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Amyloid beta-Peptides - metabolism
/ Amyloid-beta species
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Chromatography
/ Clinical trials
/ Enzyme-linked immunosorbent assay
/ Fibrils
/ Gantenerumab
/ Humans
/ Immunotherapy
/ Lecanemab
/ Monoclonal antibodies
/ Monomers
/ Neurobiology
/ Neurodegenerative diseases
/ Neurology
/ Neurosciences
/ Neurosurgery
/ Neurotoxicity
/ Oligomers
/ Original
/ Original Article
/ Peptides
/ Side effects
/ Surface plasmon resonance
/ Therapeutic antibodies
2023
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Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer's Disease
by
Osswald, Gunilla
, Eriksson, Fredrik
, Möller, Christer
, Johannesson, Malin
, Nygren, Patrik
, Laudon, Hanna
, Söderberg, Linda
, Lannfelt, Lars
in
Aducanumab
/ Aggregates
/ Alzheimer Disease - drug therapy
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Amyloid beta-Peptides - metabolism
/ Amyloid-beta species
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Chromatography
/ Clinical trials
/ Enzyme-linked immunosorbent assay
/ Fibrils
/ Gantenerumab
/ Humans
/ Immunotherapy
/ Lecanemab
/ Monoclonal antibodies
/ Monomers
/ Neurobiology
/ Neurodegenerative diseases
/ Neurology
/ Neurosciences
/ Neurosurgery
/ Neurotoxicity
/ Oligomers
/ Original
/ Original Article
/ Peptides
/ Side effects
/ Surface plasmon resonance
/ Therapeutic antibodies
2023
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Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer's Disease
by
Osswald, Gunilla
, Eriksson, Fredrik
, Möller, Christer
, Johannesson, Malin
, Nygren, Patrik
, Laudon, Hanna
, Söderberg, Linda
, Lannfelt, Lars
in
Aducanumab
/ Aggregates
/ Alzheimer Disease - drug therapy
/ Alzheimer Disease - metabolism
/ Alzheimer's disease
/ Amyloid beta-Peptides - metabolism
/ Amyloid-beta species
/ Antibodies
/ Biomedical and Life Sciences
/ Biomedicine
/ Chromatography
/ Clinical trials
/ Enzyme-linked immunosorbent assay
/ Fibrils
/ Gantenerumab
/ Humans
/ Immunotherapy
/ Lecanemab
/ Monoclonal antibodies
/ Monomers
/ Neurobiology
/ Neurodegenerative diseases
/ Neurology
/ Neurosciences
/ Neurosurgery
/ Neurotoxicity
/ Oligomers
/ Original
/ Original Article
/ Peptides
/ Side effects
/ Surface plasmon resonance
/ Therapeutic antibodies
2023
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Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer's Disease
Journal Article
Lecanemab, Aducanumab, and Gantenerumab — Binding Profiles to Different Forms of Amyloid-Beta Might Explain Efficacy and Side Effects in Clinical Trials for Alzheimer's Disease
2023
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Overview
Immunotherapy against amyloid-beta (Aβ) is a promising option for the treatment of Alzheimer's disease (AD). Aβ exists as various species, including monomers, oligomers, protofibrils, and insoluble fibrils in plaques. Oligomers and protofibrils have been shown to be toxic, and removal of these aggregates might represent an effective treatment for AD. We have characterized the binding properties of lecanemab, aducanumab, and gantenerumab to different Aβ species with inhibition ELISA, immunodepletion, and surface plasmon resonance. All three antibodies bound monomers with low affinity. However, lecanemab and aducanumab had very weak binding to monomers, and gantenerumab somewhat stronger binding. Lecanemab was distinctive as it had tenfold stronger binding to protofibrils compared to fibrils. Aducanumab and gantenerumab preferred binding to fibrils over protofibrils. Our results show different binding profiles of lecanemab, aducanumab, and gantenerumab that may explain clinical results observed for these antibodies regarding both efficacy and side effects.
Publisher
Elsevier Inc,Springer International Publishing,Springer Nature B.V
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