Angiotensin-converting enzyme gene in Alzheimer's disease.Tohoku J Exp Med 2008; 215(4):295-8TJ
Dementia has been increasing exponentially in recent years, especially in Asia. This increasing prevalence calls for the necessity of antecedent biomarkers. The angiotensin-converting enzyme (ACE) gene, located on chromosome 17q23, has been regarded as a candidate susceptibility gene for Alzheimer's disease (AD), because ACE could degrade beta-amyloid, the pathological hallmark of AD, thereby inhibiting its aggregation. The level and activity of ACE, in part, may be modulated by the insertion or deletion (indel) polymorphism of ACE gene. The indel polymorphism, consisting of the presence or absence of a 287-bp DNA fragment, has been considered the biomarker of AD, although its validity varies with race. In the Japanese, seemingly different results have been reported. One report shows significant association of insertion homozygote with AD, whereas other shows no association of indel polymorphism with AD. In the Taiwanese, the significant association of deletion homozygote with AD was found. Moreover, clinical studies have shown that using ACE inhibitors could slow the deterioration of cognitive function in AD patients, despite that ACE can degrade beta-amyloid. These heterogeneous results on the association of ACE gene with AD and clinical significance of using ACE inhibitor in AD highlight the necessity of exploring detailed mechanisms from the ACE gene to the development of AD. These detailed mechanisms and findings may serve as the basis for further study.