Global changes of phospholipids identified by MALDI imaging mass spectrometry in a mouse model of Alzheimer's disease

Abstract

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 (A β). Disrupted A β kinetics may activate intracellular signaling pathways, including tau hyperphosphorylation and proinflammatory pathways. We analyzed and visualized the lipid profi les of mouse brains using MALDI-TOF MS. Direct tissue analysis by MALDITOF 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 A β -42 ( 1 ). Our data showed changes in lipid distribution in the mouse frontal cortex, hippocampus, and subiculum, where A β 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.