Alzheimer's disease ( AD) is a complex multifactorial disorder involving a number of genetic and environmental factors. Cystatin C ( CST3), which belongs to the type II cystatin gene family, is a potent inhibitor of lysosomal proteinases. Immunohistochemical studies have demonstrated the colocalization of the b-amyloid (A- beta) and cystatin C peptides within arteriolar walls in the AD brain. The G73A polymorphism of the CST3 gene may be associated with AD development. To investigate a possible association between the CST3 G73A polymorphism and late-onset AD ( LOAD) in Mainland Chinese, we examined 281 LOAD patients and 376 healthy controls. All subjects were genotyped for CST3 and apolipoprotein E ( APOE). There were no significant differences in the CST3 genotype or allele frequencies between the cases and the controls. Likewise, with the stratification of the APOE epsilon 4 status, no statistical difference was observed between the cases and the controls. Our findings suggest that this polymorphism may not represent an additional genetic risk factor for LOAD in Mainland Chinese. Copyright (c) 2008 S. Karger AG, Basel.