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bioRxiv · 10.1101/2020.06.24.168518

Enhanced anti-amyloid effect of combined leptin and pioglitazone in APP/PS1 transgenic mice

Liu, Y.·Hanson, K. A.·McCormack, G.·Dittmann, J.·Vickers, J. C.·Fernandez-Martos, C. M.·King, A. E.
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Abstract

BackgroundAlzheimers disease (AD) has challenged single-target therapeutic strategies, raising the possibility that combined therapies may offer a more effective treatment strategy. ObjectiveThere 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 A{beta} 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. MethodsWe have re-evaluated the effects of L+P co-treatment in APP/PS1 mice using thioflavin-S staining, MOA{beta} immunolabeling and enzyme-linked immunosorbent assay (ELISA) to examine effects on A{beta} 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} (PPAR{gamma}), due to its potential role in the regulation of the inflammatory response. ResultsWe demonstrated that combining L and P significantly enhances the anti-A{beta} effect of L or P in the hippocampus of APP/PS1 mice. Western blot analysis indicated that A{beta} reduction was accompanied by up-regulation of the PPAR{gamma} levels. ConclusionOur findings suggest that combining L and P significantly enhances the anti-A{beta} effect of L or P in the hippocampus of APP/PS1 mice, and may be a potential new effective strategy for AD therapy.

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Liu, Y., Hanson, K. A., McCormack, G., Dittmann, J., Vickers, J. C., Fernandez-Martos, C. M., King, A. E.. 2020-06-24. Enhanced anti-amyloid effect of combined leptin and pioglitazone in APP/PS1 transgenic mice. https://doi.org/10.1101/2020.06.24.168518

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