An age effect on the association of common variants of ACE with Alzheimer's disease.

It is now well established that vascular risk factors are associated with cognitive performances. The renin-angiotensin system (RAS) components, major determinants of the cardiovascular system, are expressed in the brain and were shown to play a role on amyloid metabolism, learning and memory. The angiotensin-converting enzyme (ACE), a pivotal RAS protein, is encoded by a huge gene containing many variants, one of them, the I/D variant (rs1799752), being associated with Alzheimer's disease (AD). Other variants, such as SNPs rs4291A>T located -240bp from the initiation codon, and rs4343G>A encoding a silent mutation in exon 16, were inconsistently associated with the risk of AD. In a case-control study including 376 late-onset AD patients and 444 control subjects, we showed a statistically significant effect on the risk of AD of two variants (rs4343 and rs1799752) and of the haplotype ATI (rs4343/rs4291/rs1799752) in subjects aged 73 years and above.