Enhanced Anti-Amyloid Effect of Combined Leptin and Pioglitazone in APP/PS1 Transgenic Mice

Background: Alzheimer’s disease (AD) has challenged single-target therapeutic strategies, raising the possibility that combined therapies may offer a more effective treatment strategy. Objective: There is substantial evidence for the efficacy of leptin (L) (neuroprotective hormone) and pioglitazone (P) (anti-inflammatory agent) as monotherapies in AD. We have previously shown that combination treatment of L+P in APP/PS1 mice at the onset of pathology significantly improved memory and reduced brain Aβ levels relative to control mice. In this new study, we sought to replicate our previous findings in a new cohort of APP/PS1 mice to further confirm whether the combined treatment of L+P is superior to each treatment individually. Methods: We have re-evaluated the effects of L+P co-treatment in APP/PS1 mice using thioflavin-S staining, MOAβ immunolabeling, and enzyme-linked immunosorbent assay (ELISA) to examine effects on Aβ levels and pathology, relative to animals that received L or P individually. Results: We demonstrated that a combination of L and P significantly enhances the anti-Aβ effect of L or P in the hippocampus of APP/PS1 mice. Conclusion: Our findings suggest that combining L and P significantly enhances the anti-Aβ effect of L or P in the hippocampus of APP/PS1 mice and maybe a potential new effective strategy for AD therapy.