Korean J Biol Psychiatry.  2025 Oct;32(2):53-58. 10.22857/kjbp.2025.32.2.004.

The Developmental Journey and Recent Clinical Advances of Anti-Amyloid Therapies in Alzheimer’s Disease

• Youn H

• KMID: 2573754
• DOI: http://doi.org/10.22857/kjbp.2025.32.2.004

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, with rapidly growing prevalence and socioeconomic burden, particularly in aging societies such as South Korea. The amyloid cascade hypothesis has long emphasized amyloid-β (Aβ) deposition in AD pathogenesis. Many therapeutic strategies targeting Aβ production, aggregation, or clearance—such as active immunization, monoclonal antibodies (bapineuzumab, solanezumab, gantenerumab, crenezumab), and β- or γ-secretase inhibitors—failed to show meaningful clinical benefit or were halted due to safety issues including amyloid-related imaging abnormalities. Despite these setbacks, recent trials of lecanemab and donanemab demonstrated significant slowing of cognitive decline, resulting in FDA approval, with lecanemab also launched in South Korea. New candidates including remternetug, trontinemab, and sabirnetug are under development. This review summarizes the developmental history and lessons learned from anti-amyloid therapies, discusses the significance of recent advances, and considers future directions including early intervention, multi-target strategies, biomarker-based precision approaches, and health-policy implications.

Keyword

Alzheimer disease; Beta amyloid; Monoclonal antibodies; Amyloid plaques; Lecanemab; Donanemab