Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan.
Proteomics Core Laboratory, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2023 May 1;1222:123686. doi: 10.1016/j.jchromb.2023.123686. Epub 2023 Mar 30.
Alzheimer's disease (AD), the most common type of dementia, is hard to recognize early, resulting in delayed treatment and poor outcome. At present, there is neither reliable, non-invasive methods to diagnose it accurately and nor effective drugs to recover it. Discovery and quantification of novel metabolite markers in plasma of AD patients and investigation of the correlation between the markers and AD assessment scores.
Untargeted liquid chromatography-mass spectrometry (LC-MS)-based metabolomics with LC-quadrupole- time-of-flight (Q-TOF) was performed in plasma samples of age-matched AD patients and healthy controls. The potential markers were further quantified with targeted multiple reaction monitoring (MRM) approach.
Among the candidates, progesterone, and 3-indoleacetic acid (3-IAA) were successfully identified and then validated in 50 plasma samples from 25 AD patients and 25 matched normal controls with MRM approach. As a result, 3-IAA was significantly altered in AD patients and correlated with some AD assessment scores.
By using untargeted LC-MS metabolomic and LC-MRM approaches to analyze plasma metabolites of AD patients and normal subjects, 3-IAA was discovered and quantified to be significantly altered in AD patients and correlated with several AD assessment scores.
阿尔茨海默病（AD）是最常见的痴呆类型，难以早期识别，导致治疗延迟和预后不良。目前，既没有可靠的、非侵入性的方法来准确诊断，也没有有效的药物来恢复。因此，本研究旨在发现和定量 AD 患者血浆中的新型代谢标志物，并探讨标志物与 AD 评估评分之间的相关性。
采用基于液相色谱-四极杆-飞行时间（LC-Q-TOF）的非靶向液相色谱-质谱（LC-MS）代谢组学方法，对年龄匹配的 AD 患者和健康对照者的血浆样本进行分析。采用靶向多反应监测（MRM）方法对潜在标志物进行进一步定量。
在候选标志物中，孕激素和 3-吲哚乙酸（3-IAA）被成功鉴定，并进一步通过 MRM 方法在 50 例 AD 患者和 25 例匹配的正常对照者的血浆样本中进行验证。结果显示，3-IAA 在 AD 患者中明显改变，并与一些 AD 评估评分相关。
通过采用非靶向 LC-MS 代谢组学和 LC-MRM 方法分析 AD 患者和正常受试者的血浆代谢物，发现并定量了 3-IAA，其在 AD 患者中明显改变，并与多个 AD 评估评分相关。
