Hall Stephanie E, White Zachary J, Rohn Troy T, Sudasinghe Keshari H, Young Michael E
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, 1600 Denison Ave., Manhattan, KS 66506, USA.
Department of Biological Sciences, College of Arts and Sciences, Boise State University, Boise, ID 83725, USA.
Brain Sci. 2025 Jun 12;15(6):631. doi: 10.3390/brainsci15060631.
Alzheimer's disease (AD) is the third leading cause of death among older adults with nearly 6 million diagnosed annually. In the race for a cure, one thing is certain-exercise can reduce your risk. However, the mechanisms responsible for this reduced risk are unknown. Several studies have linked exercise to improved memory, reduced amyloid beta plaques, and tau hyperphosphorylation in AD. : By utilizing a novel rat model of AD, TgF344-AD, we evaluated the time course of behavioral shifts as well as the protective effect of exercise. : TgF344-AD animals (61 total, 31 females and 30 males) were assessed every 3 months from 3 to 12 months of age and then assessments were increased to monthly until they reached 18 months of age. A progressive treadmill protocol was administered at 12 months of age and continued until 18 months. Pre-intervention and post-intervention data were analyzed. : Females had greater grip strength relative to body mass compared to males and exercise attenuated the age-related and AD-induced decline. Also, female AD-impaired memory was rescued with exercise, while males had no exercise-induced improvements. : There is a sex difference present in the TgF344-AD rat model of Alzheimer's disease and this should be studied further; in addition, sex differences across all models of AD and the human pathology need to be evaluated. Exercise neuroprotection, while more prominent in females, is an important factor in AD research, and further work to understand the mechanisms of neuroprotection is warranted.
阿尔茨海默病（AD）是老年人的第三大死因，每年有近600万人被诊断出患有该病。在寻找治愈方法的过程中，有一点是肯定的——运动可以降低患病风险。然而，这种风险降低的机制尚不清楚。多项研究将运动与AD患者记忆力改善、淀粉样β斑块减少以及tau蛋白过度磷酸化联系起来。通过利用一种新型的AD大鼠模型TgF344-AD，我们评估了行为变化的时间进程以及运动的保护作用。对TgF344-AD动物（共61只，31只雌性和30只雄性）从3个月到12个月龄每3个月进行一次评估，然后评估频率增加到每月一次，直至18个月龄。在12个月龄时实施渐进式跑步机方案，并持续到18个月。对干预前和干预后的数据进行了分析。与雄性相比，雌性相对于体重具有更大的握力，运动减弱了与年龄相关的以及AD诱导的握力下降。此外，运动挽救了雌性AD受损的记忆力，而雄性则没有因运动而得到改善。在阿尔茨海默病的TgF344-AD大鼠模型中存在性别差异，这一点应进一步研究；此外，需要评估所有AD模型和人类病理学中的性别差异。运动神经保护作用虽然在雌性中更为显著，但它是AD研究中的一个重要因素，有必要进一步开展工作以了解神经保护的机制。
