Brain Areas Lipidomics in Female Transgenic Mouse Model of Alzheimer's Disease

Lipids are the major component of the brain with important structural and functional properties. Lipid disruption could play a relevant role in Alzheimer's disease (AD). Some brain lipidomic studies showed significant differences compared to controls, but few studies have focused on different brain areas related to AD. Furthermore, AD is more prevalent in females, but there is a lack of studies focusing on this sex. This work aims to perform a lipidomic study in selected brain areas (cerebellum, amygdala, hippocampus, entire cortex) from wild-type (WT, n = 10) and APPswe/PS1dE9 transgenic (TG, n = 10) female mice of 5 months of age, as a model of early AD, to identify alterations in lipid composition. A lipidomic mass spectrometry-based method was optimized and applied to brain tissue. As result, some lipids showed statistically significant differences between mice groups in cerebellum (n = 68), amygdala (n = 49), hippocampus (n = 48), and the cortex (n = 22). In addition, some lipids (n = 15) from the glycerolipid, phospholipid, and sphingolipid families were statistically significant in several brain areas simultaneously between WT and TG. A selection of lipid variables was made to develop a multivariate approach to assess their discriminant potential, showing high diagnostic indexes, especially in cerebellum and amygdala (sensitivity 70-100%, sensibility 80-100%).