A polymorphism of the interleukin-1 beta gene at position +3953 influences progression and neuro-pathological hallmarks of Alzheimer's disease

Neurobiol Aging. 2004 Sep;25(8):1017-22. doi: 10.1016/j.neurobiolaging.2003.11.002.

Abstract

Interleukin-1 (IL-1) gene polymorphisms are associated with an increased risk of Alzheimer's disease (AD) and it has been suggested that altered immune responses of the brain may play a role in the pathogenesis of the disease. Here we investigated whether IL-1beta polymorphisms affected neuro-pathological features and clinical status of AD patients with autopsy confirmed diagnosis of the disease. AD patients (n=133) were genotyped for the polymorphic regions in the apolipoprotein E epsilon (APOE epsilon) and interleukin-1beta (IL-1beta) genes. APOE epsilon4 carriers showed increased neuritic amyloid plaques (NP) and neurofibrillary tangles (NFT). The IL-1beta +3953 polymorphism influenced survival in AD patients and those with the TT genotype and without the APOE epsilon4 allele showed the shortest cumulative survival. Patients with the +3953 IL-1beta T and without the APOE epsilon4 alleles had reduced NP and NFT, a delayed ages at onset and death, but a decreased duration of the disease. On the other hand a different polymorphism of the IL-1beta gene at position -511 did not influence any AD features. Our findings suggest that IL-1beta gene by affecting brain immune responses may influence the age at onset of the disease, survival and AD progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / immunology
  • Alzheimer Disease / pathology
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Brain / immunology
  • Brain / metabolism
  • Brain / pathology
  • DNA Mutational Analysis
  • Disease Progression
  • Encephalitis / genetics*
  • Encephalitis / immunology
  • Encephalitis / pathology
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Humans
  • Interleukin-1 / genetics*
  • Interleukin-1 / immunology
  • Male
  • Neurofibrillary Tangles / genetics
  • Neurofibrillary Tangles / immunology
  • Neurofibrillary Tangles / pathology
  • Plaque, Amyloid / genetics
  • Plaque, Amyloid / immunology
  • Plaque, Amyloid / pathology
  • Point Mutation / genetics*
  • Polymorphism, Genetic / genetics*
  • Survival Rate

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Interleukin-1