The ACE gene and Alzheimer's disease susceptibility

A recent study suggested that the insertion (I) allele in intron 16 of the angiotensin converting enzyme gene (ACE) is associated with Alzheimer's dis ease (AD) risk. In our series of 239 necropsy confirmed late onset AD cases and 342 elderly non-demented controls aged >73 years, we found significant ly different ACE genotype distributions in the case and control groups (p=0 .007). Homozygotes for both the I and D alleles were associated with a high er risk compared to DI heterozygotes. While the APOE epsilon 4 allele was s trongly associated with AD risk in our series, we found no evidence for an interaction between the APOE and ACE loci. In addition, no interactions wer e observed between ACE and gender or age at death of the AD cases. A meta-a nalysis of all published reports (12 case-control series in total) suggeste d that both the II and ID ACE genotypes are associated with increased AD ri sk (odds ratio (OR) for II v DD 1.36, 95% confidence interval (CI)=1.13-1.6 3, OR for DI v DD 1.33, 95% CI=1.14-1.53, p=0.0002).