■阿尔茨海默病(AD)是一种复杂的多因素疾病,需要新的方法来阐明潜在的病理学。代谢物是基因的终产物,成绩单,和蛋白质调节,可能反映疾病的发病机理。血液是代谢组学中常用的生物流体;然而,由于细胞外囊泡(EV)持有细胞特异性生物材料,并可以通过血脑屏障,它们作为生物材料的利用值得进一步调查。我们旨在研究血液和EV衍生的代谢产物,以增加AD的病理机制。
■从10名AD和10名轻度认知障碍(MCI)患者收集血液样本,和10个健康对照。使用100,000×g从血浆中富集EV,1h,4°C洗涤。使用液相色谱-质谱(LC-MS)和核磁共振(NMR)光谱法测量血清和EV的代谢物。采用多变量和单变量分析来识别认知障碍个体中改变的代谢物。
■虽然没有发现明显的EV衍生的代谢产物可将患者与健康个体区分开来,发现六种血清代谢物很重要;缬氨酸(p=0.001,倍数变化,FC=0.8),组氨酸(p=0.001,FC=0.9),别嘌呤醇核苷(p=0.002,FC=0.2),肌苷(p=0.002,FC=0.3),4-吡啶酮酸(p=0.006,FC=1.6),和鸟苷(p=0.004,FC=0.3)。通路分析显示支链氨基酸,嘌呤和组氨酸代谢被下调,与对照组相比,患者的维生素B6代谢上调。
■使用LC-MS和NMR方法的组合,我们鉴定了可能与AD病理学相关的几种改变的机制。EV在可能用作AD相关代谢组学研究的生物材料之前需要额外的优化。
UNASSIGNED: Alzheimer\'s Disease (AD) is a complex and multifactorial disease and novel approaches are needed to illuminate the underlying pathology. Metabolites comprise the end-product of genes, transcripts, and protein regulations and might reflect disease pathogenesis. Blood is a common biofluid used in metabolomics; however, since extracellular vesicles (EVs) hold cell-specific biological material and can cross the blood-brain barrier, their utilization as biological material warrants further investigation. We aimed to investigate blood- and EV-derived metabolites to add insigts to the pathological mechanisms of AD.
UNASSIGNED: Blood samples were collected from 10 AD and 10 Mild Cognitive Impairment (MCI) patients, and 10 healthy controls. EVs were enriched from plasma using 100,000×g, 1 h, 4 °C with a wash. Metabolites from serum and EVs were measured using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Multivariate and univariate analyses were employed to identify altered metabolites in cognitively impaired individuals.
UNASSIGNED: While no significant EV-derived metabolites were found differentiating patients from healthy individuals, six serum metabolites were found important; valine (p = 0.001, fold change, FC = 0.8), histidine (p = 0.001, FC = 0.9), allopurinol riboside (p = 0.002, FC = 0.2), inosine (p = 0.002, FC = 0.3), 4-pyridoxic acid (p = 0.006, FC = 1.6), and guanosine (p = 0.004, FC = 0.3). Pathway analysis revealed branched-chain amino acids, purine and histidine metabolisms to be downregulated, and vitamin B6 metabolism upregulated in patients compared to controls.
UNASSIGNED: Using a combination of LC-MS and NMR methodologies we identified several altered mechanisms possibly related to AD pathology. EVs require additional optimization prior to their possible utilization as a biological material for AD-related metabolomics studies.