Aducanumab and Lecanemab: Target Specificity, Mechanisms and Clinical Outcomes in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is one of the major unmet medical needs as a neurodegenerative disease associated with cognitive impairment and amyloid-beta (Aβ) accumulation. Unfortunately, current drug development for AD is based on treatment with only symptomatic therapies; there is no available drug able to influence the disease process. Anti-Aβ monoclonal antibodies have been shown as the promising strategy for AD therapy. However, little is known about the dissimilarities of these drugs in terms of target, mechanisms, and clinical effects. This review discusses the differences between two anti-Aβ antibodies – aducanumab and lecanemab, including target selectivity, mechanisms of action, structure, and clinical effectiveness. In particular, this review demonstrates that aducanumab interacts with the insoluble form of the protein, causing serious side effects, whereas lecanemab selectively binds the dangerous soluble protofibrillar form of Aβ. The importance of the state of Aβ aggregation for AD treatment has been revealed through the analysis of the drugs.