The insertion polymorphism in angiotensin-converting enzyme gene associated with the APOE epsilon 4 allele increases the risk of late-onset Alzheimer disease.
The co-administration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II (AngII) receptor blockers (ARB) that bind angiotensin type 1 receptors (AT1R) may protect from Alzheimer's disease (AD) better than each treatment taken alone.
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.
Specific polymorphisms of the apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) genes appear to increase risk for Alzheimer's disease and cognitive dysfunction in the general population, yet little research has examined whether genetic factors influence risk of cognitive dysfunction in patients with Type 1 diabetes.
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.
APO-E and ACE gene polymorphisms were carried out in the patient's group only to evaluate a possible association with known genetic risk factors for AD.
These results confirm the association of the angiotensin I-converting enzyme indel with Alzheimer's disease across diverse populations, although this is probably due to linkage disequilibrium with the true risk factor.
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].
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.
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.
These results provide an important complement to existing AD risk data, confirming that ACE harbors sequence variants that contribute to aspects of AD pathology.