Genetics of interleukin 6: implications for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder that preferentially affects individuals above 60 years, with increasing risk in older ages. Neuropathological hallmarks of AD include brain atrophy, senile plaques, and neurofibrillary tangles. In addition, inflammatory processes frequently accompany the neuropathology of AD. Among several mediators of the inflammatory response, interleukin 6 (IL6) may play a role in these inflammatory processes. Polymorphisms of the IL6 gene are associated with changed IL6 gene expression, and with altered immune responses resulting in such phenotypes as early transplant rejection, the development of anti-histone antibodies in systemic lupus erythematosus, or altered bone resorption in osteoporosis. Recent data suggested that IL6 is also genetically associated with AD, but many questions remain to be answered. Which polymorphic sites can be identified within functional regions of IL6, and how do they affect gene expression, neurobiological function and pathophysiological events in health and AD? Are there interactions of other genes with IL6 that affect the development and progression of AD? Are such interactions additive, sub-additive, synergistic, or epistatic in nature? How do IL6 polymorphisms influence the therapy of AD? Answering some of these questions will be a good start toward assessing the role of IL6 in the genetics of AD.