Anti-Amyloid Monoclonal Antibodies for Alzheimer's Disease: Evidence, ARIA Risk, and Precision Patient Selection.

Abstract

Alzheimer's disease (AD) is the most common cause of dementia, pathologically defined by extracellular amyloid-β (Aβ) plaques and intracellular tau neurofibrillary tangles. Recent U.S. Food and Drug Administration (FDA) approvals of anti-amyloid monoclonal antibodies (mAbs) aducanumab, lecanemab, and donanemab represent the first disease-modifying therapies for early AD. These therapies have generated both optimism and controversy due to modest efficacy and safety concerns, particularly amyloid-related imaging abnormalities (ARIAs). This review synthesizes current evidence on the efficacy, safety, and biomarker-guided use of anti-Aβ mAbs in AD. Methods: We searched PubMed, Scopus, Web of Science, and Google Scholar to 31 July 2025 for studies on anti-amyloid mAbs in AD. Sources included peer-reviewed articles and regulatory reports. The extracted data covered study design, population, amyloid confirmation, dosing, outcomes, biomarkers, ARIA incidence, and management. Results: Anti-amyloid mAbs consistently demonstrated robust amyloid clearance and modest slowing of clinical decline in early symptomatic AD. Differences emerged across agents in efficacy signals, safety profiles, and regulatory outcomes. Lecanemab and donanemab showed more consistent cognitive benefits, while aducanumab yielded mixed findings, leading to its withdrawal. ARIAs were the most frequent adverse events, occurring more often in APOE ε4 carriers and typically during early treatment. Biomarker analyses also revealed favorable downstream effects, including reductions in phosphorylated tau and markers of astroglial injury, supporting engagement of disease biology. Conclusions: Anti-amyloid mAbs provide proof of concept for AD modification, with the greatest benefit in early disease stages and moderate tau burden. Optimal use requires biomarker confirmation of the amyloid, careful tau staging, and genetic risk assessment. While limitations remain, these therapies represent a pivotal step toward precision neurology and may serve as a foundation for multimodal strategies targeting tau, neuroinflammation, and vascular pathology.