Review: The renin-angiotensin-aldosterone system and Alzheimer's disease?

Epidemiological studies from the last decade have begun to produce evidence that the perceived joint occurrence of vascular disease and Alzheimer's disease (AD), both common elderly disorders more often believed to occur by chance due to their high prevalence, may now actually have a more pathological significance. The following review discusses some of this evidence and the implications for cognitive decline and the development of AD and how a well-known cardiovascular risk factor gene, the apolipoprotein E (APOE) gene, plays a significant role in the molecular genetics of AD. It also introduces and discusses recent and compelling evidence for the involvement of another well-known cardiovascular risk factor gene, the angiotensin-converting enzyme (ACE1) gene, in the pathogenesis of AD. This role is suggested in terms of recent molecular genetic association evidence implicating the ACE1 insertion/deletion (indel) polymorphism, a more recent large haplotype study that greatly extends the ACE1 indel evidence and incorporates knowledge accrued from previous cardiovascular disease-focused ACE1 haplotype studies. Finally, this paper discusses very recent biological evidence that further supports a role for ACE1 and hypothesises a number of readily testable mechanisms by which the ACE1 enzyme and other components of the renin-angiotensin-aldosterone system may be implicated in increased risk and/or the progression of AD.