Recent genetic, gene coexpression and imaging studies have indicated the deterioration of neurovascular integrity and altered immune responses are important steps in the initiation of Alzheimer’s disease pathogenesis. Previously we have demonstrated using mouse models that high cholesterol consumption or LDL receptor deficiency caused increase of pathological cerebral blood vessels. Recently, our focus of research is inflammatory responses. Specifically we are interested in understanding the role of inflammatory caspase-4 in Alzheimer’s disease. Inflammatory caspases mediate production of cytokines such as interleukin-1β, and induce cell death in response to a variety of pathogen and tissue damage-related molecules. Human caspase-4 is one of the inflammatory caspases and is not represented in the mouse genome. To understand the role of caspase-4, we developed a caspase-4 transgenic mouse and have characterized this model. In addition, using macrophages and microglial cells derived from various knockout mice, we are characterizing the role of various immune responses mediated by these caspases in neuronal functions.