Alzheimer’s disease (AD) is a neurodegenerative condition associated with loss of memory function, depression and anxiety. The etiology of AD is poorly understood, but both cholesterol dyshomeostasis and dysregulation of the immune system are contributing factors. Current evidence is consistent with a detrimental effect of excess cholesterol on neuroinflammation, both in mouse models of memory loss and in dementia in humans. However, whether the impact of cholesterol on neuroinflammation occurs early and contributes to pathogenesis of the disease or simply reflects a pleiotropic impact at advanced stages of disease is unclear. To explore this question, we measured, in 9–13 week-old mice, cognitive status and changes in brain inflammatory mediators in response to a short-term high-cholesterol diet. We hypothesized that short-term exposure to excess dietary cholesterol would alter the early inflammatory responses associated with cognitive and/or behavioral impairment. We report that short-term exposure to a high-cholesterol diet led to decreased thigmotaxis and short-term spatial memory impairment without affecting long-term recognition memory. Furthermore, cognitive and behavioral phenotypes in these mice were associated with a reduction in interleukin-15 levels in the absence of changes in other inflammatory mediators. Our findings indicate that interleukin-15 may play a role in early stages of cognitive impairment secondary to hypercholesterolemia. Consequently, optimization of interleukin-15 signaling may be a viable effective cognitive therapy in the population susceptible to developing dementia due to risk factors associated with cholesterol dysregulation.

阿尔茨海默病 (AD) 是一种与记忆功能丧失、抑郁和焦虑相关的神经退行性疾病。AD 的病因知之甚少，但胆固醇失调和免疫系统失调都是促成因素。目前的证据与过量胆固醇对神经炎症的不利影响一致，无论是在记忆丧失的小鼠模型中还是在人类痴呆症中。然而，胆固醇对神经炎症的影响是早期发生并有助于疾病的发病机制，还是仅仅反映了疾病晚期的多效性影响尚不清楚。为了探索这个问题，我们在 9-13 周大的小鼠中测量了认知状态和大脑炎症介质对短期高胆固醇饮食的反应。我们假设短期接触过量的膳食胆固醇会改变与认知和/或行为障碍相关的早期炎症反应。我们报告说，短期接触高胆固醇饮食会导致触感减少和短期空间记忆障碍，而不会影响长期识别记忆。此外，在其他炎症介质没有变化的情况下，这些小鼠的认知和行为表型与白细胞介素 15 水平的降低有关。我们的研究结果表明，白细胞介素 15 可能在继发于高胆固醇血症的认知障碍的早期阶段发挥作用。最后，