Association of early-onset Alzheimer's disease with an interleukin-1alpha gene polymorphism

Ann Neurol. 2000 Mar;47(3):361-5.


Overexpression of the pluripotent cytokine interleukin-1 (IL-1) by microglial cells correlates with formation of neuritic beta-amyloid plaques in Alzheimer's disease (AD). We evaluated polymorphisms in the genes coding for the IL-1alpha, IL-1beta, and IL-1 receptor antagonist cytokines, and tested their association with the occurrence and age at onset of sporadic AD. We found a strong association between the IL-1A T/T genotype and AD onset before 65 years of age (odds ratio, 4.86), with carriers of this genotype showing an onset of disease 9 years earlier than IL-1A C/C carriers. A weaker association with the age at onset was also shown for the IL-1B and IL-1RN genes. These data suggest either a direct effect of the IL-1 gene family, mainly IL-1A, on the clinical onset of AD, or a linkage dysequilibrium with an unknown locus relevant to AD on chromosome 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / etiology
  • Alzheimer Disease / genetics*
  • Female
  • Genotype
  • Humans
  • Interleukin-1 / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Risk Factors


  • Interleukin-1