Emerging Role of Donanemab in the Treatment of Early Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and memory loss, significantly impacting millions worldwide. The accumulation of amyloid-β (Aβ) plaques in the brain is a central feature of AD pathology, making it a key target for therapeutic intervention. Donanemab, a monoclonal antibody specifically designed to bind pyroglutamate-modified amyloid-β peptide (pGlu3-Aβ), has emerged as a promising disease-modifying treatment by facilitating amyloid plaque clearance via microglia-mediated phagocytosis. It has been shown in preclinical investigations to significantly reduce amyloid burden, opening the door for clinical trials. Donanemab decreased cognitive and functional deterioration in early-stage AD patients, according to Phase II and III trials, whereas Phase I trials demonstrated its safety and tolerability. After a year of treatment, about half of the patients in the TRAILBLAZER-ALZ studies showed no signs of disease progression. Donanemab is an essential step toward disease-modifying AD medications, but to optimize its therapeutic impact, more improvements in accessibility, affordability, and long-term safety are necessary. With these positive results, amyloid-related imaging abnormalities (ARIA), such as cerebral edema and microhemorrhages, continue to be a significant issue, requiring careful patient selection and monitoring. To increase effectiveness and patient compliance, future studies should investigate combination therapies that target tau proteins and neuroinflammation, optimize dosing regimens, and improve drug delivery systems.