Low circulating choline, a modifiable dietary factor, is associated with the pathological progression and metabolome dysfunction in Alzheimer’s disease
Low circulating choline, a modifiable dietary factor, is associated with the pathological progression and metabolome dysfunction in Alzheimer’s disease
Abstract Most Americans (～90%) are deficient in dietary choline, an essential nutrient. Associations between circulating choline and pathological progression in Alzheimer’s disease (AD) remain unknown. Here, we examined these associations and performed a metabolomic analysis in blood serum from severe AD, moderate AD, and healthy controls. Additionally, to gain mechanistic insight, we assessed the effects of dietary choline deficiency (Ch-) in 3xTg-AD mice and choline supplementation (Ch+) in APP/PS1 mice. In humans, we found AD-associated reductions in choline, it’s derivative acetylcholine (ACh), and elevated pro-inflammatory cytokine TNFα. Choline and ACh were negatively correlated with Plaque density, Braak stage, and TNFα, but positively correlated with MMSE and brain weight. Metabolites L-Valine, 4-Hydroxyphenylpyruvic, Methylmalonic, and Ferulic acids were associated with choline levels. In mice, Ch-paralleled AD severe, but Ch+ was protective. In conclusion, low circulating choline is associated with AD-neuropathological progression, illustrating the importance of dietary choline consumption to offset disease.
Jasbi Paniz、Beach Thomas G.、Klein-Seetharaman Judith、Serrano Geidy E.、Winslow Wendy、Velazquez Ramon、Judd Jessica M.
School of Molecular Sciences, Arizona State UniversityArizona Alzheimer?ˉs Consortium||Banner Sun Health Research InstituteSchool of Molecular Sciences, Arizona State UniversityArizona Alzheimer?ˉs Consortium||Banner Sun Health Research InstituteArizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute||Arizona Alzheimer?ˉs ConsortiumArizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute||Arizona Alzheimer?ˉs Consortium||School of Life Sciences, Arizona State UniversityArizona State University-Banner Neurodegenerative Disease Research Center at the Biodesign Institute||Arizona Alzheimer?ˉs Consortium
神经病学、精神病学生物化学基础医学
Jasbi Paniz,Beach Thomas G.,Klein-Seetharaman Judith,Serrano Geidy E.,Winslow Wendy,Velazquez Ramon,Judd Jessica M..Low circulating choline, a modifiable dietary factor, is associated with the pathological progression and metabolome dysfunction in Alzheimer’s disease[EB/OL].(2025-03-28)[2025-05-16].https://www.biorxiv.org/content/10.1101/2023.05.06.539713.点此复制
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