Passive Immunotherapies Targeting Amyloid Beta and Tau Oligomers in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is historically difficult to treat, in part because of the inaccessible nature of brain pathology. Amyloid beta and tau proteins drive pathology by forming toxic oligomers that eventually deposit as insoluble amyloid plaques and neurofibrillary tangles. Recent clinical studies suggest that effective drugs must specifically target oligomers, not native monomers or insoluble fibrils. Passive immunotherapy is a promising pharmaceutical strategy used to specifically target these oligomers in situ. Using the specificity of antibodies coupled with the natural power of the body's immune response, this treatment provides an opportunity for safe clearance of pathogenic protein species from the brain. Passive immunotherapies against amyloid beta and tau oligomers have progressed to clinical trials, with many currently in progress. Biochemical studies of antibody-oligomer complexes have helped identify previously unknown toxic epitopes, thus providing knowledge to the AD field as a whole. This mini-review focuses on the efforts to develop passive immunotherapy treatments for AD and discusses the knowledge gained from recent failures and clinical trials in progress.

Keywords: Alzheimer’s disease; CNS; amyloid beta; blood brain barrier; clearance; passive immunotherapy; protein aggregation; protein oligomers; protein structure; tau.