Hong Ji Hye, Kang Jeong Won, Kim Dong Kyu, Baik Sung Hoon, Kim Kyung Ho, Shanta Selina Rahman, Jung Jae Hun, Mook-Jung Inhee, Kim Kwang Pyo
Department of Applied Chemistry and Institute of Natural Sciences, College of Applied Sciences, Kyung Hee University, Yongin, Republic of Korea.
Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
J Lipid Res. 2016 Jan;57(1):36-45. doi: 10.1194/jlr.M057869. Epub 2015 Nov 4.
Alzheimer's disease (AD) is the most common form of dementia; however, at the present time there is no disease-modifying drug for AD. There is increasing evidence supporting the role of lipid changes in the process of normal cognitive aging and in the etiology of age-related neurodegenerative diseases. AD is characterized by the presence of intraneuronal protein clusters and extracellular aggregates of β-amyloid (Aβ). Disrupted Aβ kinetics may activate intracellular signaling pathways, including tau hyperphosphorylation and proinflammatory pathways. We analyzed and visualized the lipid profiles of mouse brains using MALDI-TOF MS. Direct tissue analysis by MALDI-TOF imaging MS (IMS) can determine the relative abundance and spatial distribution of specific lipids in different tissues. We used 5XFAD mice that almost exclusively generate and rapidly accumulate massive cerebral levels of Aβ-42 (1). Our data showed changes in lipid distribution in the mouse frontal cortex, hippocampus, and subiculum, where Aβ plaques are first generated in AD. Our results suggest that MALDI-IMS is a powerful tool for analyzing the distribution of various phospholipids and that this application might provide novel insight into the prediction of disease.
阿尔茨海默病（AD）是最常见的痴呆形式；然而，目前尚无针对AD的疾病修饰药物。越来越多的证据支持脂质变化在正常认知衰老过程以及与年龄相关的神经退行性疾病病因中的作用。AD的特征是神经元内蛋白质簇和β-淀粉样蛋白（Aβ）的细胞外聚集体的存在。Aβ动力学的破坏可能会激活细胞内信号通路，包括tau蛋白过度磷酸化和促炎通路。我们使用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）分析并可视化了小鼠大脑的脂质谱。通过MALDI-TOF成像质谱（IMS）进行直接组织分析可以确定不同组织中特定脂质的相对丰度和空间分布。我们使用了5XFAD小鼠，其几乎专门产生并迅速在大脑中积累大量的Aβ-42（1）。我们的数据显示了小鼠额叶皮质、海马体和下托中脂质分布的变化，AD中Aβ斑块首先在这些部位产生。我们的结果表明，MALDI-IMS是分析各种磷脂分布的有力工具，并且这种应用可能为疾病预测提供新的见解。
