A Novel Alzheimer's Disease Therapeutic Model: Attenuating Hyperphosphorylated Tau and Amyloid β (Aβ) Aggregates by Characterizing Antioxidative, Anti-Inflammatory, and Neuroprotective Properties of Natural Extracts

A recent line of drug failures to cure or manage Alzheimer’s disease prompted research towards discovering ways to delay the progression of this disease. Oxidative damage and neuro-inflammation were the key pathways implicated in the pathogenesis of Alzheimer’s disease. In this study, 30 natural extracts from plant roots and leaves with extensive anti-inflammatory and anti-oxidative properties were consumed by Drosophila melanogaster. In this plant extract medium, the GAL4-UAS system was used to overexpress amyloid beta (Aβ₄₂) human transgene in all the neurons of two transgenic Drosophila lines. Using Kaplan-Meier lifespan plots, 12 extracts that increased Drosophila’s lifespan the most were mixed in specific ratios to make 5 different combinational extracts. Several assays were performed to evaluate the efficacy of these combinational extracts on delaying the progression of Alzheimer’s disease. Aβ₄₂-overexpressing flies fed regular cornmeal were used as a control group, whereas Aβ₄₂-overexpressing flies fed the extract medium was used as the experimental group. In the climbing assays the experimental group showed an increased motor activity. In the lifespan assays, Kaplan-Meier plots revealed that the control group experienced a sharp decline while the experimental group showed a gradual decline. Performance index from olfactory training to evaluate the associative memory also indicated improved learning ability in the experimental group.