Analysis of the time-dependent changes of phospholipids in the brain regions of a mouse model of Alzheimer's disease.

Phospholipid levels are reported to be decreased in Alzheimer's disease (AD). For a better understanding, we investigated the time-dependent changes of phospholipids species in a mouse model of AD. The levels of phospholipids in the hippocampus and prefrontal cortex of wild-type and APP-Tg (J20) mice were measured by LC-ESI-MS/MS. Compared to wild-type, total phosphatidylcholine (PC), phosphatidylethanolamine (PE), and lysophosphatidylcholine (LPC) were Increased at 3 months but decreased at 6 months in the cortex of J20 mice. Total lysophosphatidylethanolamine (LPE) was decreased both at 3 and 6 months. PC was decreased and LPC was increased at 6 months, resulting in an increased LPC/PC ratio in the hippocampus of J20 mice. At species levels, PCA analysis could discriminate wild-type and J20 based on PC and LPC distribution at 6 months. At 6 months, several highly abundant PC including PC (16:0/16:0), PC (16:0/18:0), PC (16:0/18:1), and PC (18:0/18:1) were decreased in the cortex and hippocampus of J20. Conversely, LPC species including LPC 16:0, LPC 18:1, and LPC 20:4 were increased especially in the hippocampal area. Increased activation of phospholipid-metabolizing enzyme cPLA2 was seen in the hippocampus and cortex of J20 mice at 9 months. On the other hand, ROS levels started to increase as early as 3 months. Compared to 3 months, ROS levels were higher at 6 months in J20 mice. Thus, we demonstrated here a time- and area-dependent alteration of phospholipid composition during the early stage of AD, which could be important in understanding the pathological process.