Lecanemab and Donanemab in Early Alzheimer’s Disease: A Systematic Review of Clinical, Biomarker, and Safety Outcomes

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia worldwide. Characterized by amyloid-beta (Aβ) accumulation, tau pathology, and cognitive decline, it has long lacked effective disease-modifying treatments. Recently, monoclonal antibodies such as lecanemab and donanemab have been approved for early-stage AD, offering new therapeutic possibilities. However, differences in clinical efficacy, biomarker effects, safety outcomes, and mechanisms of action require comparative synthesis. To systematically review and compare recent evidence on lecanemab and donanemab, focusing on clinical efficacy, amyloid clearance, safety profiles, and mechanistic insights in early AD. A systematic search of PubMed and Google Scholar was conducted for peer-reviewed articles published between January 2023 and April 2025. Eligible studies included human data on Lecanemab or Donanemab in mild cognitive impairment or early AD. Nineteen DOI-verified studies were included. Data were extracted on cognitive outcomes, biomarkers, amyloid-related imaging abnormalities (ARIA) incidence, and mechanistic features. A thematic narrative synthesis was performed. Methodological quality was assessed using a modified GRADE framework. Both agents showed modest but significant slowing of cognitive decline compared to placebo. Donanemab achieved more rapid amyloid clearance, especially in intermediate tau populations, while Lecanemab demonstrated consistent reductions in p-tau181, glial fibrillary acidic protein, and neurofilament light chain. ARIA-E rates were higher for Donanemab (~24%) than for Lecanemab (~12%). Mechanistic differences included divergent Aβ binding profiles and downstream immune responses. Lecanemab and donanemab represent a major step forward in early AD treatment, though their limitations underscore the need for biomarker-guided, multitarget therapeutic strategies.