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

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.

• Authors: Federico Licastro, Fabrizio Veglia, Martina Chiappelli, Luigi Maria E Grimaldi, Eliezer Masliah
• Journal: Neurobiology of aging (Neurobiol Aging) Vol. 25 Issue 8 Pg. 1017-22 (Sep 2004) ISSN: 0197-4580 [Print] United States
• PMID: 15212826 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein E4
• Apolipoproteins E
• Interleukin-1

Topics

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