Lipids play a crucial role in the structure and physiological function of neuronal cell membranes. Brain contains large concentrations of lipids and any modification of this normal profile can result in brain dysfunction. Aging has been associated with alterations in the profile of polyunsaturated fatty acids, phospholipids and cholesterol in brain tissue. Statins are cholesterol-lowering agents that have been shown to possess neuroprotective effects (1). The molecular mechanism of this action is therefore of interest. The aim of this study was to profile lipids from young and aged rat brain tissue, and study the effect of atorvastatin with the view to understand the molecular mechanism of the latter. Young (3-4 months) and aged (22-25 months) male Wistar rats were treated with atorvastatin (5 mg/kg body weight). Lipids were extracted from brain tissue samples and analysed using high field proton nuclear magnetic resonance spectroscopy (1H-NMR) (2). Atorvatstain in brain tissue was analysed by liquid chromatography-electrospray mass spectrometry (LC-ESI-MS/MS) (3). 1H-NMR analysis indicated that there was a significant decrease in the levels of the polyunsaturated fatty acid docosahexaenoic acid, as well as choline and ethanolamine glycerophospholipids in the lipid extracts of brain tissue from aged animals as compared to the corresponding controls. Conversely, age increased the levels of cholesterol and sphingolipids in the brain of the aged animals. The atorvastatin treatment did not affect the levels of cholesterol in the brain of the aged animals. However, LC-ESI-MS/MS analysis of the atorvastatin-treated brain tissue indicated that small concentrations (0.059 ng/mg protein ± 0.018) of atorvastatin were present. Our results suggest that the age-induced alterations such as increased cholesterol in the brain lipid profiles were not reversed by the atorvastatin treatment although small amounts of atorvastatin were detected in the brain. Therefore the molecular mechanism of statin neuroprotection may be attributed to other effects and not modulation of central nervous system cholesterol homeostasis.