The pervasiveness of interleukin-1 in Alzheimer pathogenesis: a role for specific polymorphisms in disease risk

Interleukin-l (IL-l) has been implicated as a key molecule in Alzheimer pathogenesis based on findings of an IL-l overexpression in Alzheimer brain that is directly related to plaque progression and tangle formation, and on findings that IL-I induces excessive synthesis, translation, and processing of neuronal beta-amyloid precursor protein (beta APP) as well as synthesis of most known plaque-associated proteins. In addition, IL-l activates astrocytes, with the important consequence of overexpression of the neuritogenic cytokine S100 beta and overgrowth of dystrophic neurites in neuritic plaques, As further evidence of the importance of IL-l in Alzheimer pathogenesis, two new genetic studies of inheritance of specific polymorphisms in IL-l genes in Alzheimer and control patients show that homozygosity for a specific IL-IA 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-IB gene further increases risk. (C) 2000 Elsevier Science Inc. All rights reserved.