Alzheimer's disease (AD) is characterized clinically by progressive impairments in learning and memory. Accumulating evidence suggests that regular exercise plays a neuroprotective role in aging-associated memory loss. Our previous study has confirmed that long-term treadmill exercise initiated either before or during the onset of β-amyloid (Aβ) pathology, was beneficial for reducing the levels of soluble Aβ and further improved cognition. In this study, in APP/PS1 mice, we assessed changes in soluble Aβ, and various blood biochemistry and molecular biological indices to assess whether exercise modulated lipid metabolism and thereby decelerated AD progression. Our results show that long-term treadmill exercise reduced the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, and increased the level of high-density lipoprotein cholesterol. Exercise also decreased the levels of soluble Aβ1-40 and Aβ1-42, down-regulated retinoid X receptor expression, and up-regulated liver X receptor, Apolipoprotein E, Low density lipoprotein receptor, Low density lipoprotein receptor-related protein 1, and ATP-binding cassette transporter A1 expression. This indicates that long-term treadmill exercise alters the lipoprotein content, increases lipid metabolism and cholesterol transportation, reduces the soluble Aβ, and therein plays an important neuroprotective role and delays AD progression. We further show that medium exercise intensity (60%-70% of maximal oxygen uptake) was more efficacious in increasing lipid metabolism and reducing blood lipid levels and soluble Aβ levels, than low-intensity exercise (45-55% of maximal oxygen uptake). This research has broad prospects and implications, and offers a theoretical basis for the prevention of AD.

中文翻译：

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跑步机运动强度对APP / PS1小鼠海马可溶性Aβ和脂质代谢的差异作用。

临床上，阿尔茨海默氏病（AD）的特征是学习和记忆的进行性损害。越来越多的证据表明，定期运动在衰老相关的记忆丧失中起着神经保护作用。我们先前的研究已经证实，在β-淀粉样蛋白（Aβ）病理发作之前或期间开始的长期跑步机运动有益于降低可溶性Aβ的水平并进一步改善认知。在这项研究中，在APP / PS1小鼠中，我们评估了可溶性Aβ的变化以及各种血液生化和分子生物学指标，以评估运动是否能调节脂质代谢并从而减缓AD进程。我们的结果表明，长期的跑步机运动可降低总胆固醇，甘油三酸酯和低密度脂蛋白胆固醇的水平，并增加了高密度脂蛋白胆固醇的水平。运动还降低了可溶性Aβ1-40和Aβ1-42的水平，维甲酸X受体表达的下调以及肝X受体，载脂蛋白E，低密度脂蛋白受体，低密度脂蛋白受体相关蛋白1和ATP的上调结合盒转运蛋白A1的表达。这表明长期的跑步机运动会改变脂蛋白含量，增加脂质代谢和胆固醇转运，降低可溶性Aβ，并在其中起重要的神经保护作用并延迟AD进展。我们进一步表明，中等运动强度（最大摄氧量的60％-70％）在增加脂质代谢，降低血脂水平和可溶性Aβ水平方面更为有效，而不是低强度运动（最大摄氧量的45-55％）。这项研究具有广阔的前景和意义，并为预防AD提供了理论基础。