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Influence of a genetic variant of CHAT gene over the profile of plasma soluble ChAT in Alzheimer disease
Authors:Patricia Fernanda Rocha-Dias  Daiane Priscila Simao-Silva  Saritha Suellen Lopes da Silva  Mauro Roberto Piovezan  Ricardo Krause M Souza  Taher Darreh-Shori  Lupe Furtado-Alle  Ricardo Lehtonen Rodrigues Souza
Abstract:The choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) are fundamental to neurophysiological functions of the central cholinergic system. We confirmed and quantified the presence of extracellular ChAT protein in human plasma and also characterized ChAT and VAChT polymorphisms, protein and activity levels in plasma of Alzheimer''s disease patients (AD; N = 112) and in cognitively healthy controls (EC; N = 118). We found no significant differences in plasma levels of ChAT activity and protein between AD and EC groups. Although no differences were observed in plasma ChAT activity and protein concentration among ChEI-treated and untreated AD patients, ChAT activity and protein levels variance in plasma were higher among the rivastigmine-treated group (ChAT protein: p = 0.005; ChAT activity: p = 0.0002). Moreover, AD patients homozygous for SNP rs1880676 A allele exhibited higher levels of ChAT activity. Considering this is the first study to report the influence of genetic variability of CHAT locus over ChAT activity in AD patients plasma, it opens a new set of important questions on peripheral cholinergic signaling in AD.
Keywords:ChAT  VAChT  dementia  cholinergic dysfunction  peripheral cholinergic signaling
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