Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to memory loss and is often accompanied by increased anxiety. Although AD is a heterogeneous disease, dysregulation of inflammatory pathways is a consistent event. Interestingly, the amyloid precursor protein (APP), which is the source of the amyloid peptide Aβ, is also necessary for the efficient regulation of the innate immune response. Here, we hypothesize that loss of APP function in mice would lead to cognitive loss and anxiety behavior, both of which are typically present in AD, as well as changes in the expression of inflammatory mediators. To test this hypothesis, we performed open field, Y-maze and novel object recognition tests on 12–18-week-old male and female wildtype and App^KO mice to measure thigmotaxis, short-term spatial memory and long-term recognition memory. We then performed a quantitative multiplexed immunoassay to measure levels of 32 cytokines/chemokines associated with AD and anxiety. Our results showed that App^KO mice, compared to wildtype controls, experienced increased thigmotactic behavior but no memory impairments, and this phenotype correlated with increased IP-10 and IL-13 levels. Future studies will determine whether dysregulation of these inflammatory mediators contributes to pathogenesis in AD.

阿尔茨海默病 (AD) 是一种进行性神经退行性疾病，会导致记忆力减退，并且通常伴有焦虑增加。尽管 AD 是一种异质性疾病，但炎症通路的失调是一致的事件。有趣的是，淀粉样蛋白前体蛋白（APP）是淀粉样肽 Aβ 的来源，也是有效调节先天免疫反应所必需的。在这里，我们假设小鼠 APP 功能的丧失会导致认知丧失和焦虑行为，这两者通常存在于 AD 中，以及炎症介质表达的变化。为了验证这一假设，我们对 12-18 周大的雄性和雌性野生型和App ^KO进行了开放场、Y 迷宫和新物体识别测试小鼠测量趋触性、短期空间记忆和长期识别记忆。然后，我们进行了定量多重免疫测定，以测量与 AD 和焦虑相关的 32 种细胞因子/趋化因子的水平。我们的结果表明，与野生型对照相比， App ^KO小鼠的触动行为增加，但没有记忆障碍，并且这种表型与增加的 IP-10 和 IL-13 水平相关。未来的研究将确定这些炎症介质的失调是否有助于 AD 的发病机制。