Anti-Amyloid Therapies for Alzheimer's Disease: Progress, Pitfalls, and the Path Ahead.

Anti-amyloid monoclonal antibodies have finally achieved their translational breakthrough after many years of unmet expectations. The FDA granted traditional approval to lecanemab in July 2023, and the European Medicines Agency approved it in late 2024 with specific genetic restrictions; meanwhile, donanemab received FDA approval in July 2024 and EMA marketing authorization just one month ago. These agents consistently clear cerebral amyloid and slow clinical decline modestly in early-stage, biomarker-confirmed Alzheimer's disease (AD). On the other hand, they also create significant safety risks, including amyloid-related imaging abnormalities (ARIA) and substantial operational requirements for health systems that are already under pressure. Therefore, precise risk management based on APOE genotyping and the presence of cerebral amyloid angiopathy and cerebral microbleeds should be performed before therapy is initiated. The near-term agenda should prioritize the following areas of study: (1) biomarker-driven front-end triage (including emerging plasma assays); (2) ARIA-aware care pathways and shared decision making; (3) outcome-based coverage and rational pricing; (4) clinical trials that layer anti-amyloid therapy into combinatorial strategies targeting tau protein, neuroinflammation, and synaptic resilience.