Fernandez-Martos Carmen M, Atkinson Rachel A K, Chuah Meng I, King Anna E, Vickers James C
Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
Alzheimers Dement (N Y). 2016 Dec 20;3(1):92-106. doi: 10.1016/j.trci.2016.11.002. eCollection 2017 Jan.
Combination therapy approaches may be necessary to address the many facets of pathologic change in the brain in Alzheimer's disease (AD). The drugs leptin and pioglitazone have previously been shown individually to have neuroprotective and anti-inflammatory actions, respectively, in animal models.
We studied the impact of combined leptin and pioglitazone treatment in 6-month-old APP/PS1 (APPswe/PSEN1dE9) transgenic AD mouse model.
We report that an acute 2-week treatment with combined leptin and pioglitazone resulted in a reduction of spatial memory deficits (Y maze) and brain β-amyloid levels (soluble β-amyloid and amyloid plaque burden) relative to vehicle-treated animals. Combination treatment was also associated with amelioration in plaque-associated neuritic pathology and synapse loss, and also a significantly reduced neocortical glial response.
Combination therapy with leptin and pioglitazone ameliorates pathologic changes in APP/PS1 mice and may represent a potential treatment approach for AD.
联合治疗方法可能是应对阿尔茨海默病（AD）大脑中病理变化诸多方面所必需的。此前在动物模型中已分别证明，药物瘦素和吡格列酮具有神经保护作用和抗炎作用。
我们在6月龄的APP/PS1（APPswe/PSEN1dE9）转基因AD小鼠模型中研究了瘦素和吡格列酮联合治疗的影响。
我们报告称，与接受载体治疗的动物相比，瘦素和吡格列酮联合进行为期2周的急性治疗可减少空间记忆缺陷（Y迷宫实验）以及大脑β淀粉样蛋白水平（可溶性β淀粉样蛋白和淀粉样斑块负荷）。联合治疗还与斑块相关的神经病理变化和突触损失的改善有关，并且新皮质神经胶质反应也显著降低。
瘦素和吡格列酮联合治疗可改善APP/PS1小鼠的病理变化，可能代表了一种AD的潜在治疗方法。
