Alzheimer's disease (AD) is estimated to surpass cancer as the leading cause of death in the 21st century. Nonetheless, treatment options for the millions of Americans living with AD are limited to symptomatic relief that is effective in a small number of patients for a short period of time. We have taken an innovative approach to mitigating cognitive loss in AD: ameliorating the chronic, non-resolving inflammation that is characteristic of all forms of AD. The over-arching premise is that drugs which target the detrimental "cytokine cycle" that drives neuroinflammation will delay AD progression and improve the quality of life for patients. The goal of the proposed studies is to identify a humanized candidate that is suitable for clinical development and ultimately clinical trials in AD patients. This research is significant because the development of a novel class of drugs may provide new treatment options for AD patients.