Polymorphisms in inflammatory genes and the risk of Alzheimer disease

The concept of inflammation as a major factor in Alzheimer disease (AD) has hereto-fore been based on postmortem findings of autodestructive changes a ssociated with the lesions coupled with epidemiological evidence of a prote ctive effect of antiinflammatory agents.' Now there is evidence that the ri sk of AD is substantially influenced by a total of 10 polymorphisms in the inflammatory agents interleukin 1 alpha, interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, alpha (2)-macroglobulin, and alpha (1)-antich ymotrypsin. The polymorphisms are all common ones in the general population , so there is a strong likelihood that any given individual will inherit 1 or more of the high-risk alleles. The overall chances of an individual deve loping AD might be profoundly affected by a "susceptibility profile" reflec ting the combined influence of inheriting multiple high-risk alleles. Since some of the polymorphisms in question have already been linked to peripher al inflammatory disorders, such as juvenile rheumatoid arthritis, myastheni a gravis, and periodontitis, associations between AD and several chronic de generative diseases may eventually be demonstrated. Such information could lead to strategies for therapeutic intervention in the early stages of such disorders.