title: The pervasiveness of interleukin-1 in alzheimer pathogenesis: a role for specific polymorphisms in disease risk.
abstract: Interleukin-1 (IL-1) has been implicated as a key molecule in Alzheimer pathogenesis based on findings of an IL-1 overexpression in Alzheimer brain that is directly related to plaque progression and tangle formation, and on findings that IL-1 induces excessive synthesis, translation, and processing of neuronal beta-amyloid precursor protein (betaAPP) as well as synthesis of most known plaque-associated proteins. In addition, IL-1 activates astrocytes, with the important consequence of overexpression of the neuritogenic cytokine S100beta and overgrowth of dystrophic neurites in neuritic plaques. As further evidence of the importance of IL-1 in Alzheimer pathogenesis, two new genetic studies of inheritance of specific polymorphisms in IL-1 genes in Alzheimer and control patients show that homozygosity for a specific IL-1A gene polymorphism at least triples risk for development of Alzheimer's disease. This increase is associated with earlier age of onset. Homozygosity for this polymorphism plus another in the IL-1B gene further increases risk.
authors.affiliation: Departments of Geriatrics, Medicine, Psychiatry, and Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA. griffinsuet@exchange.uams.edu
authors.forename: W S
authors.initials: WS
authors.lastname: Griffin
authors.forename: J A
authors.initials: JA
authors.lastname: Nicoll
authors.forename: L M
authors.initials: LM
authors.lastname: Grimaldi
authors.forename: J G
authors.initials: JG
authors.lastname: Sheng
authors.forename: R E
authors.initials: RE
authors.lastname: Mrak
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000378:metabolism*; D011110:Polymorphism, Genetic
chemical_list: D007375:Interleukin-1