Pharmacogenetics of Angiotensin-Converting Enzyme ... - BV FAPESP
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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
de Oliveira, Fabricio Ferreira [1] ; Chen, Elizabeth Suchi [2] ; Smith, Marilia Cardoso [2] ; Ferreira Bertolucci, Paulo Henrique [1]
Total Authors: 4
Affiliation:
[1] Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Neurol & Neurosurg, Sao Paulo, SP - Brazil
[2] Fed Univ Sao Paulo UNIFESP, Escola Paulista Med, Dept Morphol & Genet, Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Current Alzheimer Research; v. 15, n. 4, p. 386-398, 2018.
Web of Science Citations: 12
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. (AU)

FAPESP's process: 15/18125-0 - Comparative analysis of cerebrospinal fluid and serum markers in dementia with Lewy bodies and Alzheimer's Disease dementia
Grantee:Paulo Henrique Ferreira Bertolucci
Support Opportunities: Regular Research Grants
FAPESP's process: 15/10109-5 - Comparative analysis of cerebrospinal fluid and serum markers in dementia with Lewy Bodies and Alzheimer's Disease dementia
Grantee:Fabricio Ferreira de Oliveira
Support Opportunities: Scholarships in Brazil - Post-Doctoral