5 years ago

Anti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease:

The majority of putative “disease-modifying” treatments in development for Alzheimer’s disease (AD) are directed against the amyloid-β (Aβ) peptide. Among the anti-Aβ therapeutic approaches, the most extensively developed is immunotherapy—and specifically, passive immunization through the administration of exogenous monoclonal antibodies (mAbs). Although the testing of mAbs has been fraught with failure and confusing results, the experience gained from these trials has provided important clues for better treatments. This review summarizes the experience to date with the anti-Aβ mAbs to enter clinical trials for AD and examines the evidence for clinical efficacy, and the major problems with safety—i.e., amyloid related imaging abnormalities (ARIA). Since mAbs differ considerably with regard to their epitopes and the conformations of Aβ that they recognize (monomers, oligomers, protofibrils, fibrils), the consequences of targeting different species are also considered. An often-cited explanation for the failure of anti-Aβ mAb trials is that they are set too late in the disease process. New trials are indeed evaluating treatments at prodromal and preclinical stages. We should expect to see additional studies of pre-symptomatic AD to join the ongoing prevention trials—for which mAbs continue to serve as the mainstay.

Publisher URL: www.sciencedirect.com/science

DOI: S0006322317318978

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