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 −240 bp 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.