Loss of APP in mice increases thigmotaxis and is associated with elevated brain expression of IL-13 and IP-10/CXCL10.

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 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 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.