Dataset Information

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

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.

SUBMITTER: Rocha-Dias PF

PROVIDER: S-EPMC7783728 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Rocha-Dias Patricia Fernanda PF Simao-Silva Daiane Priscila DP Silva Saritha Suellen Lopes da SSLD Piovezan Mauro Roberto MR Souza Ricardo Krause M RKM Darreh-Shori Taher T Furtado-Alle Lupe L Souza Ricardo Lehtonen Rodrigues RLR

Genetics and molecular biology 20201120 4

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 C ...[more]

PMID: 33306773

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Project description:Specific foods and nutrients, including alcohol, may contribute to gut barrier dysfunction. However, to our knowledge, the influence of whole diets is currently unknown. We aimed to cross-sectionally investigate associations of dietary patterns with plasma soluble CD14 (sCD14), which is released by macrophages on stimulation with endotoxin and has been used as a marker of gut hyperpermeability. We used food-frequency questionnaire data collected from 689 women in the Nurses' Health Study and 509 men in the Health Professionals Follow-Up Study. Our principal component analysis identified 2 dietary patterns: "Western" (higher intakes of red meat, processed meat, desserts, and refined grains) and "prudent" (higher intakes of fruits, vegetables, fish, and whole grains). In multivariable-adjusted logistic regression analyses, we estimated ORs and 95% CIs for high (equal to or greater than the median compared with less than the median) sCD14 concentrations in quintiles of each dietary pattern. Using logistic regression, we also investigated the joint association of the Western dietary pattern and alcohol intake or C-reactive protein (CRP) with sCD14 concentrations. Western dietary pattern scores were positively associated with sCD14 concentrations (OR: 1.86; 95% CI: 1.24, 2.79; P-trend = 0.0005; comparing extreme quintiles). Analyses of joint associations suggested that the strongest associations with higher sCD14 concentrations were for persons with both high Western pattern scores and high alcohol intake compared with participants with low scores for both (OR: 2.96; 95% CI: 1.61, 5.45) or for participants with both high Western pattern scores and high CRP values compared with those with low scores for both (OR: 4.11; 95% CI: 2.57, 6.58). The prudent pattern was not associated with sCD14 concentrations. Higher consumption of the Western dietary pattern is associated with a marker of macrophage activation and gut hyperpermeability, especially when coupled with high alcohol intake and heightened systemic inflammation. Our findings need confirmation in studies with additional markers of gut barrier dysfunction.

Dataset Information

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

Publications

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

Similar Datasets

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