College of Pharmacy, Jinan University, Guangzhou, 510632, Guangdong, China.
Postdoctoral Innovation Base, Zhuhai Yuanzhi Health Technology Co. Ltd, Hengqin New Area, Zhuhai, 519000, Guangdong, China.
Sci Rep. 2020 Sep 3;10(1):14509. doi: 10.1038/s41598-020-71510-z.
Alzheimer's Disease (AD) is closely connected to aberrant lipid metabolism. However, how early AD-like pathology synchronously influences brain and plasma lipidome in AD mice remains unclear. The study of dynamic change of lipidome in early-stage AD mice could be of great interest for the discovery of lipid biomarkers for diagnosis and monitoring of early-stage AD. For the purpose, an untargeted lipidomic strategy was developed for the characterization of lipids (≤ 1,200 Da) perturbation occurring in plasma and brain in early-stage AD mice (2, 3 and 7 months) by ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. Significant changes were detected in the levels of several lipid species including lysophospholipids, phosphatidylcholines (PCs), phosphatidylethanolamines (PEs) and Ceramides (Cers), as well as other related lipid compounds such as fatty acids (FAs), diacylglycerols (DGs) and triacylglycerols (TGs) in AD mice. In this sense, disorders of lipid metabolism appear to involve in multiple factors including overactivation of phospholipases and diacylglycerol lipases, decreased anabolism of lysophospholipids in plasma and PEs in plasma and brain, and imbalances in the levels of PCs, FAs and glycerides at different ages. We revealed the changing panels of potential lipid biomarkers with the development of early AD. The study raises the possibility of developing lipid biomarkers for diagnosis of early-stage AD.
阿尔茨海默病（AD）与异常的脂质代谢密切相关。然而，AD 小鼠早期类似 AD 的病理学如何同步影响大脑和血浆脂质组仍不清楚。研究 AD 早期小鼠脂质组的动态变化对于发现用于诊断和监测早期 AD 的脂质生物标志物可能非常有意义。为此，开发了一种非靶向脂质组学策略，用于通过超高效液相色谱与四极杆飞行时间质谱联用，对早期 AD 小鼠（2、3 和 7 个月）血浆和大脑中发生的脂质（≤1200 Da）扰动进行特征描述。在 AD 小鼠中检测到几种脂质物种水平的显著变化，包括溶血磷脂、磷脂酰胆碱（PCs）、磷脂酰乙醇胺（PEs）和神经酰胺（Cers），以及其他相关脂质化合物，如脂肪酸（FAs）、二酰基甘油（DG）和三酰基甘油（TG）。从这个意义上说，脂质代谢紊乱似乎涉及多种因素，包括磷脂酶和二酰基甘油脂肪酶过度激活、血浆中溶血磷脂和 PEs 以及血浆和大脑中 PEs 的从头合成减少，以及不同年龄 PC、FA 和甘油酯水平的失衡。我们揭示了随着早期 AD 的发展潜在脂质生物标志物的变化情况。该研究为开发早期 AD 的诊断脂质生物标志物提供了可能性。
