DNA polymorphisms of apolipoprotein B and angiotensin I-converting enzyme genes and relationships with lipid levels in Italian patients with vascular dementia or Alzheimer's disease.
A total of 400 healthy controls younger than 65 years and 350 patients with Alzheimer's disease (average age 72 years) were genotyped for the ACE and ecNOS polymorphisms.
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.
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.
We thus conclude that, in Finns, interaction between DCP1 *I and epsilon4 increases the risk of AD as well as of PD with coexisting Alzheimer pathology, which underlines the importance of the DCP1 I/D polymorphism in the development of Alzheimer neuropathology, whereas the wild type BCHE genotype in combination with epsilon4 had a combined effect with regard to the risk of AD.
To determine why ACE affects susceptibility to AD, we examined the effect of purified ACE on aggregation of the amyloid beta-peptide (A beta) in vitro.
Critical review about all studies available on DCP1 genotyping and AD, age-associated cognitive decline, longevity, and other conditions revealed remarkable inconsistencies.
Main genes involved in AD include mutational loci (APP, PS1, PS2, TAU) and multiple susceptibility loci (APOE, A2M, AACT, LRP1, IL1A, TNF, ACE, BACE, BCHE, CST3, MTHFR, GSK3B, NOS) distributed across the human genome.
We conclude therefore that the frequency of ACE I-allele is not increased in AD and, in autopsy-confirmed AD cases, possession of the ACE I allele has no impact upon the pathology of AD, at least in terms of the amount of Abeta or tau deposited in the brain.
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.
These results provide an important complement to existing AD risk data, confirming that ACE harbors sequence variants that contribute to aspects of AD pathology.
Here we report that polymorphisms within the APOE promoter, ACE1 and CYP46 gene are not risk factors for AD and are not associated with parenchymal or vascular accumulation of Abeta.
The impact of the insertion (I)/deletion (D) (I/D) polymorphism in the angiotensin 1-converting enzyme (ACE) gene on the extent of white matter myelin loss (ML) was investigated in four regions of the cerebral cortex in an autopsy-confirmed series of 93 patients with Alzheimer's disease (AD).
Cell-specific effects of ACE polymorphism are suggested, additional studies on neuronal cells might help to understand the role of this polymorphism in AD.