Fabricio Ferreira de Oliveira, Sandro Soares de Almeida, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci
{"title":"Pharmacogenetics of angiotensin modulators according to <i>APOE</i>-ϵ4 alleles and the <i>ACE</i> insertion/deletion polymorphism in Alzheimer's disease.","authors":"Fabricio Ferreira de Oliveira, Sandro Soares de Almeida, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci","doi":"10.1017/neu.2023.38","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>In Alzheimer's disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-β by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-β-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the <i>ACE</i> insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (<i>APOE</i>)-ϵ4 carrier status and blood pressure response to angiotensin modulators.</p><p><strong>Methods: </strong>Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking <i>APOE</i>-ϵ4 carrier status and genotypes of the <i>ACE</i> insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs.</p><p><strong>Results: </strong>For 193 patients (67.4% women, 53.4% <i>APOE</i>-ϵ4 carriers), the <i>ACE</i> insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (<i>p</i> = 0.281), while arterial hypertension was prevalent in 80.3% (<i>n</i> = 124 used an ACEi, <i>n</i> = 21 used an ARB). ARBs benefitted mostly <i>APOE</i>-ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted <i>APOE</i>-ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The <i>ACE</i> insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations.</p><p><strong>Conclusion: </strong>Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.</p>","PeriodicalId":7066,"journal":{"name":"Acta Neuropsychiatrica","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Neuropsychiatrica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/neu.2023.38","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 1
Abstract
Objective: In Alzheimer's disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-β by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-β-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the ACE insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (APOE)-ϵ4 carrier status and blood pressure response to angiotensin modulators.
Methods: Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking APOE-ϵ4 carrier status and genotypes of the ACE insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs.
Results: For 193 patients (67.4% women, 53.4% APOE-ϵ4 carriers), the ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (p = 0.281), while arterial hypertension was prevalent in 80.3% (n = 124 used an ACEi, n = 21 used an ARB). ARBs benefitted mostly APOE-ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted APOE-ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The ACE insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations.
Conclusion: Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.
期刊介绍：
Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.
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