Influence of a genetic variant of CHAT gene over the profile of plasma soluble ChAT in Alzheimer disease

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 polymor...

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Bibliographic Details
Published in:	Genetics and molecular biology Vol. 43; no. 4; p. e20190404
Main Authors:	Rocha-Dias, Patricia Fernanda, Simao-Silva, Daiane Priscila, Silva, Saritha Suellen Lopes da, Piovezan, Mauro Roberto, Souza, Ricardo Krause M, Darreh-Shori, Taher, Furtado-Alle, Lupe, Souza, Ricardo Lehtonen Rodrigues
Format:	Journal Article
Language:	English
Published:	Brazil Sociedade Brasileira de Genética 01-01-2020
Subjects:	BIOCHEMISTRY & MOLECULAR BIOLOGY ChAT cholinergic dysfunction dementia GENETICS & HEREDITY Human and Medical Genetics Medicin och hälsovetenskap peripheral cholinergic signaling VAChT ChAT dementia peripheral cholinergic signaling cholinergic dysfunction VAChT
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Associate Editor: Filippo Pinto e Vairo Authors Contributions: RLRS, LFA, PFRD, DSSS, conceived and the study; PFRD, DPSS, SSLS conducted the experiments; TDS, RLRS, PFRD, DPSS analyzed the data; PFRD, DPSS, RLRS, LFA, TDS wrote the manuscript; MRP, RKMS made the clinical diagnosis. All authors read and approved the final version. Conflict of Interest: The authors declare that there is no conflict of interest that could be perceived as prejudicial to the impartiality of the reported research.
ISSN:	1415-4757 1678-4685 1678-4685
DOI:	10.1590/1678-4685-GMB-2019-0404