Knörnschild Franz, Zhang Ella J, Ghosh Biswas Rajshree, Kobus Marta, Chen Jiashang, Zhou Jonathan X, Rao Angela, Sun Joseph, Wang Xiaoyu, Li Wei, Muti Isabella H, Habbel Piet, Nowak Johannes, Xie Zhongcong, Zhang Yiying, Cheng Leo L
Departments of Radiology and Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Anesthesia, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Transl Psychiatry. 2025 Mar 18;15(1):87. doi: 10.1038/s41398-025-03293-8.
Alzheimer's disease (AD) is a complex, progressive neurodegenerative disorder, impacting millions of geriatric patients globally. Unfortunately, AD can only be diagnosed post-mortem, through the analysis of autopsied brain tissue in human patients. This renders early detection and countering disease progression difficult. As AD progresses, the metabolomic profile of the brain and other organs can change. These alterations can be detected in peripheral systems (i.e., blood) such that biomarkers of the disease can be identified and monitored with minimal invasion. In this work, High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy is used to correlate biochemical changes in mouse brain tissues, from the cortex and hippocampus, with blood plasma. Ten micrograms of each brain tissue and ten microliters of blood plasma were obtained from 5XFAD Tg AD mice models (n = 15, 8 female, 7 male) and female C57/BL6 wild-type mice (n = 8). Spectral regions-of-interest (ROI, n = 51) were identified, and 121 potential metabolites were assigned using the Human Metabolome Database and tabulated according to their trends (increase/decrease, false discovery rate significance). This work identified several metabolites that impact glucose oxidation (lactic acid, pyruvate, glucose-6-phosphate), allude to oxidative stress resulting in brain dysfunction (L-cysteine, galactitol, propionic acid), as well as those interacting with other neural pathways (taurine, dimethylamine). This work also suggests correlated metabolomic changes within blood plasma, proposing an avenue for biomarker detection, ideally leading to improved patient diagnosis and prognosis in the future.
阿尔茨海默病（AD）是一种复杂的、进行性神经退行性疾病，全球影响着数百万老年患者。不幸的是，AD只能在死后通过对人类患者尸检脑组织的分析来诊断。这使得早期检测和对抗疾病进展变得困难。随着AD的进展，大脑和其他器官的代谢组学特征会发生变化。这些改变可以在外周系统（即血液）中检测到，从而可以以最小的侵入性识别和监测疾病的生物标志物。在这项工作中，高分辨率魔角旋转（HRMAS）核磁共振（NMR）光谱用于将小鼠大脑皮层和海马组织中的生化变化与血浆相关联。从5XFAD转基因AD小鼠模型（n = 15，8只雌性，7只雄性）和雌性C57/BL6野生型小鼠（n = 8）中获取10微克每种脑组织和10微升血浆。确定了感兴趣的光谱区域（ROI，n = 51），并使用人类代谢组数据库分配了121种潜在代谢物，并根据它们的趋势（增加/减少，错误发现率显著性）制成表格。这项工作确定了几种影响葡萄糖氧化的代谢物（乳酸、丙酮酸、6-磷酸葡萄糖），暗示氧化应激导致脑功能障碍（L-半胱氨酸、半乳糖醇、丙酸），以及那些与其他神经通路相互作用的代谢物（牛磺酸、二甲胺）。这项工作还表明血浆中存在相关的代谢组学变化，为生物标志物检测提供了一条途径，理想情况下有望在未来改善患者的诊断和预后。
