Amyloid beta (Abeta)-induced neurotoxicity is a major pathological mechanism of Alzheimer disease (AD). In this study, we investigated the inhibitory effect of l-theanine, a component of green tea (Camellia sinensis), on Abeta(1-42)-induced neuronal cell death and memory impairment. Oral treatment of l-theanine (2 and 4 mg/kg) for 5 weeks in the drinking water of mice, followed by injection of Abeta(1-42) (2 microg/mouse, icv), significantly attenuated Abeta(1-42)-induced memory impairment. Furthermore, l-theanine reduced Abeta(1-42) levels and the accompanying Abeta(1-42)-induced neuronal cell death in the cortex and hippocampus of the brain. Moreover, l-theanine inhibited Abeta(1-42)-induced extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase as well as the activity of nuclear factor kappaB (NF-kappaB). l-Theanine also significantly reduced oxidative protein and lipid damage and the elevation of glutathione levels in the brain. These data suggest that the positive effects of l-theanine on memory may be mediated by suppression of ERK/p38 and NF-kappaB as well as the reduction of macromolecular oxidative damage. Thus, l-theanine may be useful in the prevention and treatment of AD.