Mice deficient in acetylcholinesterase (AChE; EC3.1.1.7) exhibited significant phenotypical and biochemical changes when compared with wild-type littermates. They showed a delay of growth in weight and size, immature external ears, and persistent body tremor, and they circled when walking. The molecular mechanisms underlying these changes have not been investigated yet. Here, we studied the profiles of both the messenger RNA (mRNA) and protein expression in the brain of AChE-deficient mice using mRNA microarray, quantitative PCR, and two-dimensional difference gel electrophoresis (2D DIGE) coupled to protein identification with matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) mass spectrometry. Analysis of gene expression profile was conducted by DAVID ( http://david.abcc.ncifcrf.gov ) and Ingenuity Pathway Analysis (IPA, http://www.ingenuity.com ). Previous results implicated that there is a close relationship between lipid metabolisms which were associated with central nervous system development. Here, we demonstrated that the mRNA expressions of brain specific fatty acid protein 7 (fabp-7) and phospholipase A2 group IV (pla2g4) were significantly downregulated in AChE-deficient mice. These results suggested that AChE may play a role in neurogenesis and neurodegeneration by specifically regulating lipid metabolism in the brain.