PPAR gamma agonist reduces amyloid pathology in aged senescence mice model : mechanisms involving LRP1 expression

Abstract

Objective. The role of peroxisome proliferator-activated receptor-γ (PPAR-γ) activation in Alzheimer’s disease (AD) is still controversial. Low-density lipoprotein receptor-related protein 1 (LRP1) is known to play an important role in secretion of amyloid-β (Aβ) in AD. The current study is carried out to investigate the effect of pioglitazone, PPAR-γ agonist, on Aβ deposition, LRP1 expression, and memory impairment in a senescence mouse model.Methods. Pioglitazone was orally administrated to 9-month-old SAMP8 mice in variable doses (0.5 mg/kg/day, 2 mg/kg/day and 5 mg/kg/day) for 7 weeks. Memory function was assessed using Morris water maze test. Aβ deposition and LRP1 expression in mice brain were investigated.Results. Pioglitazone treatment showed improvement in memory impairment. Pioglitazone-treated SAMP8 mice showed reduced Aβ deposition than vehicle-treated mice. In addition, increased LRP1 expression in microvessel was observed in pioglitazone-treated SAMP8 mice.Conclusion. These results suggest that pioglitazone may provide a protective effect against memory impairment through increasing LRP1 expression in blood-brain barrier and reducing Aβ deposition. Pioglitazone could have a therapeutic potential for the treatment of AD.