Amyloid-β-targeting immunotherapies for Alzheimer's disease

Recent advances in clinical passive immunotherapy have provided compelling evidence that eliminating amyloid-beta (A beta) slows cognitive decline in Alzheimer's disease (AD). However, the modest benefits and side effects observed in clinical trials indicate that current immunotherapy therapy is not a panacea, highlighting the need for a deeper understanding of AD mechanisms and the significance of early intervention through optimized immunotherapy or immunoprevention. This review focuses on the centrality of A beta pathology in AD and summarizes recent clinical progress in passive and active immunotherapies targeting A beta, discussing their lessons and failures to inform future anti-A beta biotherapeutics design. Various delivery strategies to optimize A beta-targeting immunotherapies are outlined, highlighting their benefits and drawbacks in overcoming challenges such as poor stability and limited tissue accessibility of anti-A beta biotherapeutics. Additionally, the perspectives and challenges of immunotherapy and immunoprevention targeting A beta are concluded in the end, aiming to guide the development of next-generation anti-A beta immunotherapeutic agents towards improved efficacy and safety.