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

Exp Gerontol. 2000 Jul;35(4):481-7. doi: 10.1016/s0531-5565(00)00110-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Genetic Predisposition to Disease*
  • Humans
  • Interleukin-1 / genetics*
  • Interleukin-1 / metabolism*
  • Polymorphism, Genetic*

Substances

  • Interleukin-1