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.