Riaz_2026_Health.Sci.Rep_9_e72688

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition marked by the accumulation of beta-amyloid plaques and neurofibrillary tangles, leading to neuronal death and cognitive decline. Acetylcholinesterase inhibitors (AChEIs) such as donepezil, galantamine, and rivastigmine are commonly used to enhance cognitive function by increasing acetylcholine levels, but they can cause side effects like nausea, bradycardia, and headaches. NMDA receptor antagonists, like memantine, reduce glutamatergic activity and are used to manage symptoms, yet are also associated with adverse effects including dizziness and agitation. Recently, monoclonal antibodies such as aducanumab have been developed to target amyloid-beta aggregates, though they are associated with amyloid-related imaging abnormalities (ARIA). AIMS: This article aims to summarize current pharmacological approaches to AD and to highlight the emerging role of Donanemab-azbt, an FDA-approved monoclonal antibody for early symptomatic AD, in reducing amyloid plaques and slowing cognitive decline. METHODS: This overview synthesizes data from clinical trials and therapeutic experience with acetylcholinesterase inhibitors, NMDA receptor antagonists, and monoclonal antibodies, with a particular focus on Donanemab-azbt, its mechanism of targeting amyloid-beta aggregates, and its efficacy and safety profile in early symptomatic AD. RESULTS: Donanemab-azbt has demonstrated efficacy in clinical trials, significantly reducing amyloid plaque burden and slowing cognitive decline in patients with early symptomatic AD. However, its use may result in ARIA and other adverse effects, necessitating careful clinical and radiological monitoring during treatment. CONCLUSION: Despite the risks of ARIA and other adverse events, Donanemab-azbt represents a promising addition to AD therapy, offering the potential for improved outcomes in patients with early symptomatic disease and expanding the therapeutic options beyond traditional symptomatic treatments.