Ogunsuyi_2025_Neurodegener.Dis.Manag__1

BACKGROUND: Despite emerging therapeutic options, Alzheimers disease (AD) management remains suboptimal due to multimodal pathogenesis. We investigated curcumin-donepezil combination therapy, as curcumin demonstrates antioxidant, anti-inflammatory, and anti-amyloidogenic properties that may complement donepezil's cholinesterase inhibition. RESEARCH DESIGN AND METHODS: We employed the elav-Gal4/UAS-hAPP-BACE-1 Drosophila melanogaster model alongside molecular docking simulation and ADMET prediction to evaluate curcumin-donepezil combination versus monotherapy. Fruit flies received the treatment regimen, and were tested for survival, memory performance, and biochemical markers, including BACE-1 activity and oxidative stress parameters. RESULTS: Combination therapy significantly improved survival rates and memory performance compared to individual treatment. The combination effectively modulated multiple AD-related pathways, demonstrating reduced BACE-1 activity and decreased oxidative stress markers. Molecular docking confirmed favorable drug interactions, and ADMET profiles supported therapeutic viability. CONCLUSIONS: Curcumin-donepezil combination therapy shows promise as a multi-target approach for AD management. However, translation to clinical applications requires validation in higher-order models and human trials.