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

Overexpression of the pluripotent cytokine interleukin-l (IL-I) by microgli al cells correlates with formation of neuritic P-amyloid plaques in Alzheim er's disease (AD). We evaluated polymorphisms in the genes coding for the I L-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 y ears of age (odds ratio, 4.86), with carriers of this genotype showing an o nset of disease 9 years earlier than IL-1A CIC carriers. A weaker associati on with the age at onset was also shown for the IL-1B and IL-1RN genes. The se data suggest either a direct effect of the IL-I gene family, mainly IL-1 A, on the clinical onset of AD, or a linkage dysequilibrium with an unknown locus relevant to AD on chromosome 2.