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.
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.
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.
In search for a treatment approach of AD, we found that inhibition of the angiotensin-converting enzyme (ACE) by a centrally acting ACE inhibitor retards symptoms of neurodegeneration, Abeta plaque formation and tau hyperphosphorylation in experimental models of AD.
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.
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.
Moreover it altered the Aβ mediated pathways, lifespan, macromolecular damage and down regulated the AD related gene expression of ace-1, hsp-4 and Aβ, thereby preventing Aβ synthesis.
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.
Moreover, patients with aMCI could take ACE inhibitor (ACEI) to decrease the incidence of AD, and patients with AD could take ACEI to retard cognitive decline in early AD.
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.
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.
Overall, we observe significant association with risk for AD and polymorphisms in ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2 [rs1859849].