Microglia are special cells in the brain that play a key role in Alzheimer’s disease (AD). Even though a lot of research has been done to understand how microglia respond to AD, we still do not fully know how they interact with other brain cells and how they contribute to damage in brain cells. Our main goal is to explore how human microglia affect brain cell connections and damage in a living organism. Human microglia are different from those in mice, especially regarding certain genes linked to Alzheimer’s, which makes it important to study them in humans. Some behaviours of these cells are also hard to study in lab dishes because they involve complicated interactions with other cells. In XenoMicrogliaAD, we will use a new model that we developed, which allows us to transplant human microglia into mouse systems, and examine how they affect brain health. Specifically, we will look at two main ways microglia might harm brain cells: by removing connections between cells and by releasing substances that can lead to cell damage. To do this, we will use advanced techniques to study how human microglia interact with brain cells and what substances they produce in the context of Alzheimer’s disease. The project will help map how microglia interact with synapses (connections between brain cells) in both healthy brains and those affected by Alzheimer’s disease. It will also explore the interactions between human microglia and brain cells in living systems, and identify the specific substances produced by these microglia in Alzheimer’s disease. This research will be the first to deeply investigate the role of human microglia in Alzheimer’s disease at this level of detail, potentially leading to new treatments and ways to detect and tackle the disease.
