Microglia, as the resident immune cells in the brain, serve many crucial functions related to long-term health. There are many molecular signals exchanged between neurons and microglia that establish and maintain homeostasis. In Alzheimer’s disease (AD), these signals are disrupted, which results in changes in microglial function. Microglia in AD overeat synapses, the connections between neurons, as well as whole neurons, and this loss of neurons and their connections leads to loss of memory and cognitive ability. The signals leading to disruptions in normal microglial function in AD are largely unknown. One signal released specifically by neurons known to be important for regulating microglia is interleukin-34 (IL-34). This molecule is important for maintaining appropriate numbers of microglia within the brain and potentially other microglial functions as well. Interestingly, a mutation in the IL-34 gene was recently identified as a risk factor for developing AD. In line with this, decreased levels of IL-34 have been identified in human brains affected by AD, as well as in mouse models of AD. It is the primary goal of our experiments to identify the role of IL-34 signaling in AD, specifically in the context of microglia-neuron interactions. Furthermore, we hope to test whether overexpressing IL-34 in a mouse model of AD rescues molecular and behavioral deficits, which would establish IL-34 as a therapeutic target for treating AD.