In this study, we explore the effects of altered angiotensin-converting enzyme (ACE), and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD.
The insertion polymorphism in angiotensin-converting enzyme gene associated with the APOE epsilon 4 allele increases the risk of late-onset Alzheimer disease.
This suggests a modest but significant increase in risk of AD and early AD pathology in women homozygous for the ACE I-allele independent of vascular factors.
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.
In conclusion, our data suggest that the ACE allelic variant is not a susceptibility factor in sporadic and familial AD (FAD), nor does it mitigate the effect of the APOE epsilon4 allele in the risk of developing AD.
The risk of AD was also significant for people with ACE DD genotype, D allele, or T-D haplotype [OR (95% CI) = 4.29 (1.96-10.23), 1.90 (1.35-2.70), or 2.91 (1.71-5.10), respectively].
Cell-specific effects of ACE polymorphism are suggested, additional studies on neuronal cells might help to understand the role of this polymorphism in AD.
Gender-specific risk for AD has been previously reported, and a biological rationale for involvement of ACE in the AD process is supported by studies exploring the relationship between AD and vascular risk factors such as hypertension.
Using multivariate logistic regression analysis, we found that in diagnosed AD cases there was a significant interaction between ApoE4 and ACE inhibitor use (odds ratio: 20.85; 95% confidence interval: 3.08-140.95; p = 0.002) after adjusting for age, sex, ethnicity, and education.
This study was aimed to estimate variations of measures of cardiovascular risk in Alzheimer's dementia by pharmacogenetic analyses of the effects of angiotensin-converting enzyme (ACE) inhibitors and statins.
To investigate the possible relationship between genetic risk factors and depression in AD, we assessed genetic polymorphisms reported to be associated with depression (MAOA VNTR, ACE 288bp Insertion/ Deletion, 5HTTLPR, COMT Val158Met, BDNF Val66Met, TPH1 A218C, HTR2A T102C, P2RX7 Q460R, FKBP5 rs1360780 and CRHR1 rs242941) in a cross-sectional study on 246 AD patients with or without clinically significant major depressive disorder (MDD) according to DSM-IV.