Antibody-Based Drugs and Approaches Against Amyloid-β Species for Alzheimer’s Disease Immunotherapy

Jing Liu, Bin Yang, Jun Ke, Wenjia Li, Wen-Chen Suen

Alzheimer's disease (AD), one of the most devastating diseases for the older population, has become a major healthcare burden in the increasingly aging society worldwide. Currently, there are still only symptomatic treatments available on the market, just to slow down disease progression. In the past decades, extensive research focusing on the development of immunotherapy using monoclonal antibodies (mAbs) as potential "disease-modifying drugs" has shown promise in inhibiting or clearing the formation of toxic amyloid-β (Aβ) species, the suspected causative agents of AD. As a result, these potential life-saving drugs can break the amyloid cascade, cease neurodegeneration, and prevent further reduction in cognitive and physical function. In this review, we first describe the polymorphisms of Aβ species, comprising three different pools, including monomers, soluble oligomers, and insoluble fibrils, with each pool encompassing multiple structures of Aβ aggregation. A comprehensive review on their toxicities follows in relation to the characterized epitopes of anti-Aβ mAb candidates under development. We then present the outcomes of these mAbs in clinical or pre-clinical trials and conclude by providing a summary of other novel and promising antibody-based immunotherapeutic approaches that deserve more attention for the effective treatment of AD in the future.