DOCK2 Is a Microglial Specific Regulator of Central Nervous System Innate Immunity Found in Normal and Alzheimer’s Disease Brain

Neuroinflammation is a hallmark of several neurode-generative diseases, including Alzheimer’s disease (AD). Strong epidemiological and experimental evi-dence supports the use of nonsteroidal anti-inflam-matory drugs to reduce AD risk. However, poor out-come in clinical trials and toxicity in a prevention trial have shifted focus away from these cyclooxygen-ase (COX) inhibitors to seek additional therapeutic targets in the prostaglandin pathway. Previously, the prostaglandin E2 receptor, EP2, was shown to regu-late neuroinflammation and reduce A plaque burden in transgenic mice. Unfortunately, widespread EP2 distribution and a direct effect on COX2 induction make EP2 a less desirable target. In this study, we link dedicator of cytokinesis 2 (DOCK2) to the prostaglan