Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Diets high in fat also increase disease neuropathology and/or cognitive deficits in AD mouse models. However, the effect of a high-fat diet on both the neuropathology and memory impairments in the triple-transgenic mouse model of AD (3xTgAD) is unknown. Therefore, groups of 2-month-old male 3xTgAD and control (non-Tg) mice were maintained on a high-fat or control diet and memory was assessed at the age of 3-4, 7-8, 11-12, and 15-16 months using a series of behavioral tests. A comparable increase in body weight was observed in non-Tg and 3xTgAD mice after high-fat feeding at all ages tested but a significantly greater increase in epididymal adipose tissue was observed in 3xTgAD mice at the age of 7-8, 11-12, and 15-16 months. A high-fat diet caused memory impairments in non-Tg control mice as early as the age of 3-4 months. In 3xTgAD mice, high-fat consumption led to a reduction in the age of onset and an increase in the extent of memory impairments. Some of these effects of high-fat diet on cognition in non-Tg and 3xTgAD mice were transient, and the age at which cognitive impairment was detected depended on the behavioral test. The effect of high-fat diet on memory in the 3xTgAD mice was independent of changes in AD neuropathology as no significant differences in (plaques, oligomers) or tau neuropathology were observed. An acute increase in microglial activation was seen in high-fat fed 3xTgAD mice at the age of 3-4 months but in non-Tg control mice microglial activation was not observed until the age of 15-16 months. These data indicate therefore that a high-fat diet has rapid and long-lasting negative effects on memory in both control and AD mice that are associated with neuroinflammation, but independent of changes in beta amyloid and tau neuropathology in the AD mice.

译文

众所周知,肥胖和高脂饮食会增加患阿尔茨海默氏病 (AD) 的风险。高脂肪饮食还会增加AD小鼠模型的疾病神经病理学和/或认知缺陷。然而,在AD (3xTgAD) 的三重转基因小鼠模型中,高脂饮食对神经病理学和记忆障碍的影响尚不清楚。因此,将2个月大的雄性3xtgad和对照组 (非Tg) 小鼠维持高脂或对照饮食,并在3-4、7-8、11-12岁时评估记忆力,15-16个月使用一系列行为测试。在所有测试年龄的高脂喂养后,在非Tg和3xtgad小鼠中观察到体重的可比增加,但在7-8岁的3xtgad小鼠中观察到附睾脂肪组织的显着增加,11-12和15-16个月。高脂饮食早在3-4个月大时就导致非Tg对照小鼠的记忆力障碍。在3xtgad小鼠中,高脂肪消耗导致发病年龄的减少和记忆障碍程度的增加。高脂饮食对非Tg和3xtgad小鼠认知的某些影响是短暂的,检测到认知障碍的年龄取决于行为测试。高脂饮食对3xtgad小鼠记忆的影响与AD神经病理学的变化无关,因为未观察到 (斑块,低聚物) 或tau神经病理学的显着差异。在3-4个月大时,高脂喂养的3xTgAD小鼠中观察到小胶质细胞活化的急性增加,但在非Tg对照小鼠中,直到15-16个月大时才观察到小胶质细胞活化。因此,这些数据表明,高脂饮食对与神经炎症相关的对照组和AD小鼠的记忆具有快速而持久的负面影响,但与AD小鼠的 β 淀粉样蛋白和tau神经病理学的变化无关。

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