['To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD.', 'A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls.', 'The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE epsilon4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset.'] Is a polymorphism in the cystatin C gene a novel risk factor for late-onset Alzheimer 's disease?