阿尔茨海默病的免疫治疗——不良反应的挑战

Department of Neurology, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, China

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. © 2012 Macmillan Publishers Limited. All rights reserved.

Wang, Y.-J.; Department of Neurology, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, China; email:yanjiang_wang@tmmu.edu.cn