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

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

Author de Oliveira, Fabricio Ferreira Autor UNIFESP Google Scholar
Chen, Elizabeth Suchi Autor UNIFESP Google Scholar
Smith, Marilia Cardoso Autor UNIFESP Google Scholar
Ferreira Bertolucci, Paulo Henrique Autor UNIFESP Google Scholar
Abstract Background: While the angiotensin-converting enzyme degrades amyloid-beta, angiotensin-converting 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.
Keywords Alzheimer disease
drug therapy
neurodegenerative diseases
renin-angiotensin system
xmlui.dri2xhtml.METS-1.0.item-coverage Sharjah
Language English
Sponsor CAPES - Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [1067/10]
FAPESP - The State of Sao Paulo Research Foundation [2015/10109-5, 2015/18125-0]
Grant number CAPES [1067/10]
FAPESP [2015/10109-5, 2015/18125-0]
Date 2018
Published in Current Alzheimer Research. Sharjah, v. 15, n. 4, p. 386-398, 2018.
ISSN 1567-2050 (Sherpa/Romeo, impact factor)
Publisher Bentham Science Publ Ltd
Extent 386-398
Access rights Closed access
Type Article
Web of Science ID WOS:000426616800009

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