The bioactive lipids plasmalogens (Pls), especially the ethanolamine types, PlsEtn, are found to be enriched in the central nervous system (CNS). Previous reports showed that the brain and serum Pls levels were reduced in Alzheimer's disease (AD). However, the role of the Pls in AD is mostly elusive. Furthermore Pls have been suggested to have pathophysiological significance in ageing and stress responses in the CNS, which often involve neuroinflammation characterized by glial cell activation. Focusing on these lipids function in the murine brain, we first show that Pls can ameliorate microglial activation induced by systemic inflammatory stimuli. Then their protective effects on the neuronal cell death are demonstrated. The precise mechanism of how these lipids function in the brain is now under investigation but our study will reveal the myth of these crucial lipid components in the CNS. Future study also could suggest novel therapeutics to safeguard our brain from various stresses including ageing, neuroinflammation as well as the memory disturbance in AD.