title: Effect of APOE and CHRNA7 genotypes on the cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease.
abstract: The loss of cholinergic transmission is considered to be an important cause of Alzheimer's disease (AD). Treatment with acetyl cholinesterase inhibitors (ChEIs) shows benefits; however, great heterogeneity has been observed in patient responses. We evaluated apolipoprotein E (APOE) and α7 nicotinic receptor (CHRNA7) single-nucleotide polymorphisms (SNPs) and associated these SNPs with pharmacological responses to ChEIs in a Brazilian population with AD. We studied 177 outpatients using ChEIs, and they were classified as responders and nonresponders according to variation in Mini-Mental State Examination (MMSE) status. The analysis of APOE genotypes showed that patients with the ε4 allele had a worse response than those without the ε4 allele. We observed an association between the CHRNA7 T allele and a better response to treatment with ChEIs in patients with mild AD (MMSE ≥ 20). The SNP rs6494223 of CHRNA7 as well as APOEε4 could be useful for understanding the response to ChEI treatment in patients with AD.
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil.
authors.forename: Ianna Lacerda Sampaio
authors.initials: IL
authors.lastname: Braga
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil.
authors.forename: Patricia Natalia
authors.initials: PN
authors.lastname: Silva
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil.
authors.forename: Tatiane Katsue
authors.initials: TK
authors.lastname: Furuya
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil.
authors.forename: Leonardo Caires
authors.initials: LC
authors.lastname: Santos
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil.
authors.forename: Belisa Caldana
authors.initials: BC
authors.lastname: Pires
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil.
authors.forename: Diego Robles
authors.initials: DR
authors.lastname: Mazzotti
authors.affiliation: Disciplina de Neurologia Clínica, Departamento de Neurologia e Neurocirurgia (UNIFESP), São Paulo-SP, Brazil.
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Bertolucci
authors.affiliation: Disciplina de Geriatria e Gerontologia, Departamento de Medicina (UNIFESP), São Paulo-SP, Brazil.
authors.forename: Maysa Seabra
authors.initials: MS
authors.lastname: Cendoroglo
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo-SP, Brazil macsmith.morf@epm.br.
authors.forename: Marília Cardoso
authors.initials: MC
authors.lastname: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001938:Brazil; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016896:Treatment Outcome; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics*
chemical_list: D053327:Apolipoprotein E4; D002800:Cholinesterase Inhibitors; C579167:Chrna7 protein, human; D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: APOE; Alzheimer’s disease; CHRNA7; cholinesterase inhibitor; pharmacogenomics