Polymorphisms in Inflammatory Genes and the Risk of Alzheimer Disease

Open Access
Publisher Website
Google Scholar
Abstract
The concept of inflammation as a major factor in Alzheimer disease (AD) has heretofore been based on postmortem findings of autodestructive changes associated with the lesions coupled with epidemiological evidence of a protective effect of anti-inflammatory agents.1 Now there is evidence that the risk of AD is substantially influenced by a total of 10 polymorphisms in the inflammatory agents interleukin 1α, interleukin 1β, interleukin 6, tumor necrosis factor α, α2-macroglobulin, and α1-antichymotrypsin. 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 developing AD might be profoundly affected by a "susceptibility profile" reflecting the combined influence of inheriting multiple high-risk alleles. Since some of the polymorphisms in question have already been linked to peripheral inflammatory disorders, such as juvenile rheumatoid arthritis, myasthenia gravis, and periodontitis, associations between AD and several chronic degenerative diseases may eventually be demonstrated. Such information could lead to strategies for therapeutic intervention in the early stages of such disorders.