Cathepsin D is the major lysosomal/endosomal aspartic protease and exhibits beta- and gamma-secretase-like activity in vitro. Data from German suggest that the C224T polymorphism in the Cathepsin D gene (CTSD) exon 2 is strongly associated with the risk for Alzheimer's disease (AD). Meanwhile other studies have not been able to replicate the result. It's necessary to determine the genotype of the polymorphism in CTSD in Chinese sporadic AD patients and age-matched controls with normal cognition and examine possible association of the polymorphism with the disease. We find no strong evidence of association between the CTSD C224T polymorphism and Chinese sporadic AD. Whereas there may be a weak synergistic interaction between ApoE epsilon4 and CTSD T allele.