Comparison of the effects of lithium orotate and lithium carbonate on locomotion and memory in a Drosophila melanogaster model of Alzheimer’s disease

Alzheimer’s disease (AD) is a terminal neurodegenerative disease characterized by cognitive decline and memory loss resulting from the buildup of amyloid-beta plaques and tau protein tangles. Lithium salts, particularly lithium carbonate (Li₂CO₃), inhibit the enzyme Glycogen Synthase Kinase-3, which is upregulated in AD, reducing tau and amyloid-beta accumulation, inflammation, and oxidative stress. However, Li₂CO₃ has declined in use due to long-term neurotoxicity. Lithium orotate (LiOr), an alternative lithium salt, has greater bioavailability–delivering more ions to the brain–but was discontinued in the 1970s due to toxicity concerns at equivalent doses. It was hypothesized that LiOr would be more effective than Li₂CO₃ at lower doses (5 mM) due to higher lithium ion transfer, while Li₂CO₃ may outperform LiOr at higher doses (10 mM) due to LiOr’s toxicity. This study compares LiOr and Li₂CO₃ in treating locomotion and memory in a Drosophila melanogaster model produced by crossing UAS amyloid-beta 42 and Act5c GAL4 flies via the GAL4/UAS system. Once aged to 25 days, flies were assessed for locomotion using the negative geotaxis assay and for short-term memory using the aversive phototaxic suppression (APS) assay. These behavioral assays aim to quantify changes in cognitive and motor function resulting from treatment. Results suggest Li₂CO₃ improves cognitive and motor performance in healthy flies, but LiOr was not found to be significantly more effective. This study offered a novel comparison of two lithium compounds in an Alzheimer’s model and may guide research into safer, more effective AD and lithium treatments.