A polymorphism of the interleukin-1 beta gene at position +3953 influences progression and neuro-pathological hallmarks of Alzheimer's disease.
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.
Licastro
Federico
F
Department of Experimental Pathology, University of Bologna, Bologna, Italy. licastro@alma.unibo.it
Veglia
Fabrizio
F
Chiappelli
Martina
M
Grimaldi
Luigi Maria E
LM
Masliah
Eliezer
E
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004660:Encephalitis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics* / Q000276:immunology; D008297:Male; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000276:immunology / Q000473:pathology; D058225:Plaque, Amyloid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D015996:Survival Rate
D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D007375:Interleukin-1