Interleukin-1, neuroinflammation, and Alzheimer's disease.
Interleukin-1 (IL-1)-1) is a pluripotent immunomodulatory cytokine that has an initiating role in cellular and humoral immunity in the periphery. Il-1 is overexpressed in Alzheimer brain, and this overexpression is directly related to plaque formation and progression, nonsensical growth of dystrophic neurites, and neuronal overexpression of acetylcholinesterase. IL-1 has a number of actions relevant to Alzheimer's disease, including excessive expression of neuronal Abeta precursor protein and other plaque-associated proteins, and induction of astrocyte activation and astrocytic overexpression of S100B. These latter events may be related to the overgrowth of dystrophic neurites in neuritic plaques, a necessary event for conversion of diffuse Abeta deposits into the neuritic amyloid plaques diagnostic of Alzheimer's disease. Four new genetic studies underscore the relevance of IL-1 to Alzheimer pathogenesis, showing that homozygosity of a specific polymorphism in the IL-1A gene at least triples Alzheimer risk, especially for an earlier age of onset and in combination with homozygosity for another polymorphism in the IL-1B gene.
Mrak
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Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. mrakroberte@uams.edu
Griffin
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D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001923:Brain Chemistry / Q000235:genetics / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D007375:Interleukin-1 / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000473:pathology*; D011110:Polymorphism, Genetic / Q000235:genetics
D007375:Interleukin-1