Hippocampus Proteomics and Brain Lipidomics Reveal Network Dysfunction and Lipid Molecular Abnormalities in APP/PS1 Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is closely associated with protein dysfunction and aberrant lipid metabolism in the brain. Our study could be conducive to the discovery of lipid and protein biomarkers for early diagnosis and therapy. In our current work, novel quantitative proteomic and lipidomic methods were developed for the characterization of molecular perturbation occurring in the brain in early stage AD mice. For this purpose, we performed a proteomic and lipidomic screening by liquid chromatography with mass spectrometry. Significant changes were detected, including 231 proteins and 11 lipid compounds in the AD mouse brain. Early stage AD disturbed biological pathways implicated in neuroactive ligand-receptor, complement and coagulation cascades, PI3K-Akt signaling and metabolic pathways, and glycerophospholipid metabolism. The results in the current study suggest that these significantly altered proteins and lipids may be implicated in early stage AD. Our work raises the possibility of AD diagnosis and therapy by providing new protein targets and lipid biomarkers.