Overexpression of the pluripotent cytokine interleukin-l (IL-I) by microglial cells correlates with formation of neuritic P-amyloid plaques in Alzheimer's disease (AD). We evaluated polymorphisms in the genes coding for the IL-1 alpha, IL-IP, 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-IA 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 CIC 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-I 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.
Grimaldi, L., Casadei, V., Ferri, C., Veglia, F., Licastro, F., Annoni, G., et al. (2000). Association of Early-Onset Alzheimer¿s Disease with an Interleukin-1 alpha Polymorphism. ANNALS OF NEUROLOGY, 47(3), 361-365 [10.1002/1531-8249(200003)47:3<361::AID-ANA12>3.0.CO;2-N].
Association of Early-Onset Alzheimer¿s Disease with an Interleukin-1 alpha Polymorphism
ANNONI, GIORGIO;
2000
Abstract
Overexpression of the pluripotent cytokine interleukin-l (IL-I) by microglial cells correlates with formation of neuritic P-amyloid plaques in Alzheimer's disease (AD). We evaluated polymorphisms in the genes coding for the IL-1 alpha, IL-IP, 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-IA 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 CIC 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-I 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.
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