血管紧张素转换酶抑制剂在阿尔茨海默病痴呆患者中的药物遗传学

Title:Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia

Volume: 15 Issue: 4

关键词: 阿尔茨海默病，痴呆，药物疗法，神经退行性疾病，神经精神病学，药物遗传学，肾素血管紧张素系统

摘要: Background: While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer’s disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification.

Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis.

Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 – C (44.6% heterozygotes) and 0.345 for rs4291 – T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 – T and rs4291 – A, or for APOE4- carriers of rs1800764 – T or rs4291 – T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis.

Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes.

Cite this article as:

Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia, Current Alzheimer Research 2018; 15 (4) . https://dx.doi.org/10.2174/1567205014666171016101816