Genetic polymorphisms in the cathespin D and interleukin-6 genes and the risk of Alzheimer's disease

Alzheimer's disease (AD) is a complex multi-factorial disease with the invo lvement of several possible genes. The apolipoprotein E*4 (APOE*4) allele o f the known susceptibility gene, APOE, is neither necessary,nor sufficient to cause AD. This has prompted the search for other candidate genes associa ted with the risk of AD. Cathepsin D (Cat D) is an intracellular aspartyl p rotease that has been reported to have in vitro beta and gamma-secretase ac tivity. The presence of a C --> T (Ala --> Val) polymorphism in exon 2 of t he Cat D gene has been reported to be associated with an increased risk of AD. Further, as inflammation is reported to play a prominent role is AD pat hogenesis, IL-6, a known mediator of inflammation, is another candidate gen e proposed to be associated with the risk of AD. Genetic variation in the I L-6 gene has been reported to be associated with the risk of AD. We perform ed a genetic screening of sporadic, late-onset AD cases and age-matched con trols to evaluate the role of Cat D and IL-6 polymorphisms in AD. Our data indicate no significant association between these polymorphisms and the ris k of AD. When the data were stratified by APOE*4 status, no significant dif ference was seen either between cases and controls. These data suggest that the Cat D and IL-6 polymorphisms do not significantly alter the risk of AD in our case-control cohort. (C) 2000 Elsevier Science Ireland Ltd. All rig hts reserved.