18 - The Possible Role of Brain Inflammation in Alzheimer’s Disease May Be More Significant in APOE-4 Carriers

Summary

There has been growing evidence of the importance of inflammation in Alzheimer’s disease. Briefly, there have been a number of observations that people taking anti-inflammatory medications, particularly those with rheumatoid arthritis, may have a modestly reduced risk of getting Alzheimer’s disease. Studies in animal models have shown that brain inflammation has a dual response, protective in the acute reaction and detrimental when chronic. In these animal studies, chronic neuroinflammation activates inflammatory cells in the brain called microglia, increases beta-amyloid burden, and increases the production of hyperphosphorylated tau, the toxic form of tau protein found in neurofibrillary tangles. However, trials of anti-inflammatory medications such as ibuprofen in humans have for the most part failed to show a significant reduction in the risk of getting Alzheimer’s. Recent work has suggested that this damaging effect of inflammation on Alzheimer’s risk does indeed occur in humans but is specific to those carrying the APOE-4 allele.