Grant: Project Grant

This study will explore how exposure to natural living environments shapes the immune system and influences the progression and treatment of Alzheimer's disease (AD) in mouse models. Our goal is to create more realistic models of AD to improve the development of effective therapies. While the immune system plays a critical role in AD, most research relies on mice born and raised in ultra-clean lab settings, which do not reflect the diverse environmental exposures that humans experience. To address this, we have created a novel "rewilding" platform that mimics natural ecosystems - complete with farm soil, plants, and insects - within a controlled indoor vivarium. Common AD mice exposed to this environment show profound changes in immune cell populations, including B cells, T cells, and brain-resident microglia. Using multiple AD mouse models, we will examine how rewilding affects hallmark disease features, including brain plaques, tau tangles, inflammation, and blood-brain barrier integrity. We will apply cognitive testing, advanced immune profiling, and high-resolution imaging to assess these changes. We will also evaluate whether a more mature, environmentally shaped immune system reduces side effects of AD immunotherapies (such as inflammation or swelling in the brain) that limit their current use in patients. This research will provide new insights into how immune system maturity influences brain health and treatment outcomes. By improving the relevance of mouse models to human disease, our findings could accelerate the development of safer, more effective therapies for Alzheimer's disease, ultimately supporting healthier aging.