The genetic association between cathepsin D and Alzheimer's disease

The aspartyl protease Cathepsin D has previously been suggested to play a role in the Alzheimer's disease (AD) process because of its ability to cleave the P-amyloid precursor protein and the possibility that it may be one of the 'secretase' enzymes. A functional C double right arrow T polymorphism in the Cathepsin D gene (CATD) has been reported to be associated with increased risk for AD in Caucasian case-control studies; specifically, the T-carrying genotypes confer increased risk. We have examined this association in our own Caucasian dataset of 210 AD cases and 120 controls, and in an additional Hispanic dataset comprising 79 AD cases a nd 112 controls. In Hispanics we fi nd a modest interaction between CATD genotype and age of onset on risk for AD, such that the non-T-carrying genotype confers increased risk. In our Caucasian dataset we find no evidence for association between the CATD polymorphism and AD, although we do observe a small tendency towards an increase in the T-carrying genotypes in the case group, consistent with previous studies. We conducted an aggregate analysis of the published Caucasian datasets and found evidence that this CATD polymorphism (or another locus in linkage disequilibrium) does contribute significant, but small (<2%) risk for AD. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.