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.
Our results suggest that APOE and ACE genotypes may be independent risk factors for late-onset AD, but the ACE association needs to be confirmed in independent samples in which the time and extent of vascular cofactors can be assessed.
The frequency of the ACE*ins allele was also greater in the groups with Alzheimer's disease and dementia in general (P = 0.022; P = 0.045), but genotype frequencies were only different in groups without the E*4/-317*ins haplotype (P = 0.012 for Alzheimer's disease; P = 0.04 for dementia).
N-domain of angiotensin-converting enzyme hydrolyzes human and rat amyloid-β(1-16) peptides as arginine specific endopeptidase potentially enhancing risk of Alzheimer's disease.
We evaluated the association between 15 single-nucleotide polymorphisms (SNPs) in DCP1, including the I/D variant, and AD in a sample of 92 patients with AD and 166 nondemented controls from an inbred Israeli Arab community.
Critical review about all studies available on DCP1 genotyping and AD, age-associated cognitive decline, longevity, and other conditions revealed remarkable inconsistencies.
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.
We measured Ang-II and Ang-III levels by ELISA, and the levels and activities of aminopeptidase-A (AP-A) and aminopeptidase-N (AP-N) (responsible for the production and metabolism of Ang-III, respectively) in human postmortem brain tissue in the mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59), for which we had previous measurements of ACE-1 activity, Aβ level, and tau pathology (also in the mid-frontal cortex).