Judd Jessica M, Jasbi Paniz, Winslow Wendy, Serrano Geidy E, Beach Thomas G, Klein-Seetharaman Judith, Velazquez Ramon
bioRxiv. 2023 May 8:2023.05.06.539713. doi: 10.1101/2023.05.06.539713.
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.
大多数美国人（约90%）膳食中胆碱缺乏，胆碱是一种必需营养素。循环胆碱与阿尔茨海默病（AD）病理进展之间的关联尚不清楚。在此，我们研究了这些关联，并对重度AD、中度AD患者及健康对照者的血清进行了代谢组学分析。此外，为深入了解其机制，我们评估了3xTg-AD小鼠膳食胆碱缺乏（Ch-）和APP/PS1小鼠胆碱补充（Ch+）的影响。在人类中，我们发现AD患者的胆碱、其衍生物乙酰胆碱（ACh）减少，促炎细胞因子TNFα升高。胆碱和ACh与斑块密度、Braak分期及TNFα呈负相关，但与MMSE及脑重量呈正相关。代谢产物L-缬氨酸、4-羟基苯丙酮酸、甲基丙二酸和阿魏酸与胆碱水平相关。在小鼠中，Ch-与AD严重程度相似，但Ch+具有保护作用。总之，循环胆碱水平低与AD神经病理进展相关，说明膳食中摄入胆碱对缓解疾病的重要性。
