Pharmacogenetics of angiotensin modulators according to APOE-ϵ4 alleles and the ACE insertion/deletion polymorphism in Alzheimer's disease
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:35 |
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| Enthalten in: |
Acta neuropsychiatrica - 35(2023), 6 vom: 11. Dez., Seite 346-361 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Oliveira, Fabricio Ferreira de [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.12.2023 Date Revised 16.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1017/neu.2023.38 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361045581 |
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| 100 | 1 | |a Oliveira, Fabricio Ferreira de |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacogenetics of angiotensin modulators according to APOE-ϵ4 alleles and the ACE insertion/deletion polymorphism in Alzheimer's disease |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 16.12.2023 | ||
| 500 | |a Date Revised 16.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a CONCLUSION: Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Alzheimer disease | |
| 650 | 4 | |a drug therapy | |
| 650 | 4 | |a neurodegenerative diseases | |
| 650 | 4 | |a pharmacogenetics | |
| 650 | 4 | |a renin-angiotensin system | |
| 650 | 7 | |a Angiotensin Receptor Antagonists |2 NLM | |
| 650 | 7 | |a Angiotensin-Converting Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a Angiotensins |2 NLM | |
| 650 | 7 | |a Apolipoproteins E |2 NLM | |
| 700 | 1 | |a Almeida, Sandro Soares de |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Elizabeth Suchi |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Marilia Cardoso |e verfasserin |4 aut | |
| 700 | 1 | |a Bertolucci, Paulo Henrique Ferreira |e verfasserin |4 aut | |
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