Alzheimer's disease (AD) is characterized by a progressive deterioration of cognitive function, however, current therapeutic approaches have shown limited clinical utility. Aberrantly increased inflammation is also pathological hallmark of AD. Recent data show that in both humans and animal models of disease, neutrophils, key players in the innate immune response, drive AD via the formation of Neutrophil Extracellular Traps (NETs), a pro-inflammatory form of cell death. Aberrant NET formation is also a hallmark of other chronic systemic inflammatory diseases including rheumatoid arthritis (RA), lupus, ulcerative colitis, and atherosclerosis. This pro-inflammatory form of cell death results in the extrusion of chromatin to form a web-like structure that promotes blood clotting, inflammation, and more generally leads to collateral tissue damage by releasing redox generating enzymes (i.e., MPO), active proteases (e.g., neutrophil elastase), and cytokines. NET formation requires histone citrullination to facilitate the unraveling and extrusion of chromatin fibers. Histone citrullination is catalyzed by the Protein Arginine Deiminases (PADs). Notably, PAD inhibitors demonstrate remarkable efficacy in a range of NET driven diseases including RA, lupus, ulcerative colitis, and atherosclerosis. PAD inhibitors also show efficacy in other diseases, including multiple sclerosis, hypoxic ischemia, and spinal cord injury whose etiology may also involve aberrant NET formation. Given the evidence supporting a role for neutrophils and NET formation in the etiology of AD, the PIs seek to test the hypothesis that blocking NET formation via the use of PAD inhibitors represents a viable approach to treat AD.