期刊
BIOLOGICAL PSYCHIATRY
卷 83, 期 4, 页码 311-319出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2017.08.010
关键词
Alzheimer's disease; Amyloid-beta; Amyloid-beta oligomers; Amyloid-related imaging abnormalities; Immunotherapy; Monoclonal antibodies
资金
- National Institute on Aging [P50-AG047270]
- National Center for Advancing Translational Science [UL1-TR000142]
- Janssen Pharmaceuticals, Inc.
- Eli Lilly and Company
- Genentech, Inc.
- Merck and Co.
- Novartis International AG
- Toyama
- Pfizer Inc.
- Forum Pharmaceuticals
- TauRx Therapeutics Ltd.
- Eisai Co., Ltd.
- Hoffman-La Roche
- Biogen, Inc.
The majority of putative disease-modifying treatments in development for Alzheimer's disease are directed against the amyloid-beta (A beta) peptide. Among the anti-A beta therapeutic approaches, the most extensively developed is immunotherapy-specifically, passive immunization through administration of exogenous monoclonal antibodies (mAbs). Although 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 anti-Ab mAbs to enter clinical trials for Alzheimer's disease and examines the evidence for clinical efficacy and the major problems with safety-i.e., amyloid-related imaging abnormalities. As mAbs differ considerably with regard to their epitopes and the conformations of Ab 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-Ab 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 presymptomatic Alzheimer's disease to join the ongoing prevention trials, for which mAbs continue to serve as the mainstay.
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