title: Immunotherapy for Alzheimer disease: the challenge of adverse effects.
abstract: Amyloid-β (Aβ) plays a crucial part in the pathogenesis of Alzheimer disease (AD), making this peptide an attractive therapeutic target. However, clearance of brain Aβ in clinical trials of Aβ-specific antibodies did not improve cognition in patients with AD, leading to reassessment of the current therapeutic strategies. Moreover, current immunotherapies are associated with autoimmunity-related adverse effects, and mobilization of neurotoxic insoluble Aβ-oligomers. Despite the fact that antibodies to the N-terminal domain of Aβ can promote Aβ production, immunotherapies in ongoing clinical trials predominantly target this peptide region. Here, we address the challenges of adverse effects of immunotherapy for AD. We discuss available evidence regarding the mechanisms of both endogenous and exogenous Aβ-specific antibodies, with a view to developing optimal immunotherapy based on peripheral Aβ clearance, targeting of the toxic domain of Aβ, and improvement of antibody specificity. Such strategies should help to make immunotherapy a safe and efficacious disease-modifying treatment option for AD.
authors: Department of Neurology and Centre for Clinical Neuroscience, Daping Hospital and Institute of Field Surgery, Third Military Medical University, Yuzhong District, Chongqing, China.
authors: Yu-Hui
authors: YH
authors: Liu
authors: Brian
authors: B
authors: Giunta
authors: Hua-Dong
authors: HD
authors: Zhou
authors: Jun
authors: J
authors: Tan
authors: Yan-Jiang
authors: YJ
authors: Wang
mesh_terms: D000544:Alzheimer Disease / Q000276:immunology* / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000906:Antibodies / Q000009:adverse effects / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects*
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies