The present study investigated an ethanol extract of Chaenomeles sinensis fruit (CSF) for possible neuroprotective effects on neurotoxicity induced by amyloid β protein (Aβ) (25-35) in cultured rat cortical neurons and also for antidementia activity in mice. Exposure of cultured cortical neurons to 10μM Aβ (25-35) for 36 h induced neuronal apoptotic death. At 0.1-10μg/ml, CSF inhibited neuronal death, elevation of intracellular calcium concentration ([Ca2+]i), and generation of reactive oxygen species (ROS) induced by Aβ (25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of mice with 15 nmol Aβ (25-35) was inhibited by chronic treatment with CSF (10, 25 and 50 mg/kg, p.o. for 7 days) as measured by a passive avoidance test. CSF (50 mg/kg) inhibited the increase of cholinesterase activity in Aβ (25-35)-injected mice brain. From these results, we suggest that the antidementia effect of CSF is due to its neuroprotective effect against Aβ (25-35)-induced neurotoxicity and that CSF may have a therapeutic role for preventing the progression of Alzheimer's disease.