Grant: Travel Awards - Institute Community Support

Background: Neuroinflammation, or inflammation in the brain, is a well known feature of Alzheimer's Disease (AD). The resolution, or ending, of inflammation was recently found to be mediated by a class of molecules derived from long chain omega-3s fatty acids, the fats found in fish, presenting a mechanism for the protective role of fish consumption on AD that have been noted in observational studies. Objectives: 1) To characterize how inflammation initiates and resolves in a mouse model of AD and 2) To determine the role of omega-3s in modulating this process. Methods: Amyloid-beta, a protein thought to be a cause of AD, will be injected into the brains of mice. This has been shown to cause cognitive impairment and inflammation in previous studies. Objective 1: Brains were collected 1-28 days post-surgery and inflammation measured by immunohistochemistry. Objective 2: Experiments were repeated in mice deficient in omega-3s, and in a transgenic and dietary model of optimal omega-3 status. Inflammation was measured using immunohistochemistry and a microarray, while the fatty acid makeup of the brain was measured with thin layer and gas chromatography. Results: Inflammation and its resolution in this model of AD was found to peak between 10 and 15 days post-surgery, returning to baseline by 28 days. The mice on an omega-3 deficient diet experienced greater brain inflammation upon amyloid-beta injection than the mice with sufficient omega-3s. Pathways of gene expression associated with inflammation were also increased in the deficient mice, but not in mice with higher brain levels of omega-3s. Conclusions: Omega-3 fatty acids are protective against the neuroinflammatory component of Alzheimer's Disease in this model. Implications: This work provides a mechanism to explain the protective effects of omega-3 consumption on AD development that have been seen previously. This could lead to better informed dietary recommendations and potential new therapeutic targets.