Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.24.168518v1?rss=1 Authors: Liu, Y., Hanson, K. A., McCormack, G., Dittmann, J., Vickers, J. C., Fernandez-Martos, C. M., King, A. E. Abstract: Background: Alzheimers 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 previouly shown that combination treatment of L+P in APP/PS1 mice at the onset of pathology significantly improved memory and reduced brain Abeta levels relative to control mice. In this new study, we sought to replicate our previous findings in a new cohort of APP/PS1 mouse 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, MOAbeta immunolabeling and enzyme-linked immunosorbent assay (ELISA) to examine effects on Abeta levels and pathology, relative to animals that received L or P individually. To explore mechanism of regulation, we used Western blotting to examine the expression of the peroxisome-proliferator activated receptor gamma (PPARgamma), due to its potential role in the regulation of the inflammatory response. Results: We demonstrated that combining L and P significantly enhances the anti-Abeta effect of L or P in the hippocampus of APP/PS1 mice. Western blot analysis indicated that Abeta reduction was accompanied by up-regulation of the PPARgamma levels. Conclusion: Our findings suggest that combining L and P significantly enhances the anti-Abeta effect of L or P in the hippocampus of APP/PS1 mice, and may be a potential new effective strategy for AD therapy. Copy rights belong to original authors. Visit the link for more info