title: Amyloid beta peptide immunotherapy in Alzheimer disease.
abstract: Recent advances in the understanding of Alzheimer's disease pathogenesis have led to the development of numerous compounds that might modify the disease process. Amyloid β peptide represents an important molecular target for intervention in Alzheimer's disease. The main purpose of this work is to review immunotherapy studies in relation to the Alzheimer's disease. Several types of amyloid β peptide immunotherapy for Alzheimer's disease are under investigation, active immunization and passive administration with monoclonal antibodies directed against amyloid β peptide. Although immunotherapy approaches resulted in clearance of amyloid plaques in patients with Alzheimer's disease, this clearance did not show significant cognitive effect for the moment. Currently, several amyloid β peptide immunotherapy approaches are under investigation but also against tau pathology. Results from amyloid-based immunotherapy studies in clinical trials indicate that intervention appears to be more effective in early stages of amyloid accumulation in particular solanezumab with a potential impact at mild Alzheimer's disease, highlighting the importance of diagnosing Alzheimer's disease as early as possible and undertaking clinical trials at this stage. In both phase III solanezumab and bapineuzumab trials, PET imaging revealed that about a quarter of patients lacked fibrillar amyloid pathology at baseline, suggesting that they did not have Alzheimer's disease in the first place. So a new third phase 3 clinical trial for solanezumab, called Expedition 3, in patients with mild Alzheimer's disease and evidence of amyloid burden has been started. Thus, currently, amyloid intervention is realized at early stage of the Alzheimer's disease in clinical trials, at prodromal Alzheimer's disease, or at asymptomatic subjects or at risk to develop Alzheimer's disease and or at asymptomatic subjects with autosomal dominant mutation.
authors.affiliation: Alzheimer's Disease Clinical Research Centre, Gérontopôle, Toulouse University Hospital, 170, avenue de Casselardit, 31059 Toulouse cedex 9, France. Electronic address: delrieu.j@chu-toulouse.fr.
authors.forename: J
authors.initials: J
authors.lastname: Delrieu
authors.affiliation: Alzheimer's Disease Clinical Research Centre, Gérontopôle, Toulouse University Hospital, 170, avenue de Casselardit, 31059 Toulouse cedex 9, France; Inserm 1027, Faculté de médecine, 37, allées Jules-Guesde, 31000 Toulouse, France.
authors.forename: P J
authors.initials: PJ
authors.lastname: Ousset
authors.affiliation: Alzheimer's Disease Clinical Research Centre, Gérontopôle, Toulouse University Hospital, 170, avenue de Casselardit, 31059 Toulouse cedex 9, France; Inserm 1027, Faculté de médecine, 37, allées Jules-Guesde, 31000 Toulouse, France.
authors.forename: T
authors.initials: T
authors.lastname: Voisin
authors.affiliation: Alzheimer's Disease Clinical Research Centre, Gérontopôle, Toulouse University Hospital, 170, avenue de Casselardit, 31059 Toulouse cedex 9, France; Inserm 1027, Faculté de médecine, 37, allées Jules-Guesde, 31000 Toulouse, France.
authors.forename: B
authors.initials: B
authors.lastname: Vellas
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000379:methods; D055808:Drug Discovery / Q000639:trends; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C550616:solanezumab; C545458:bapineuzumab
keywords: Alzheimer's disease; Amyloid β peptide; Anticorps monoclonaux; Biomarkers; Biomarqueurs; Immunotherapy; Immunothérapie; Maladie d’Alzheimer; Monoclonal antibodies; Peptide β amyloïde; Vaccin; Vaccine