Effects of soybean-derived phosphatidylinositol (PI) on amyloid beta protein (10 nM Abeta(25-35))-induced changes in Cl(-)-ATPase activity, intracellular Cl- concentration ([Cl-]i) and glutamate neurotoxicity were examined using cultured rat hippocampal neurons. Soybean-derived PI (> or =5 nM) dose-dependently recovered Abeta-induced decrease in neuronal Cl(-)-ATPase activity without any changes in the activities of Na+,K(+)-ATPase and anion-insensitive Mg(2+)-ATPase. Soybean-derived PI reduced Abeta-induced elevation of [Cl-](i) as assayed using a Cl(-)-sensitive fluorescent dye, and prevented Abeta-induced aggravation of glutamate neurotoxicity assayed by mitochondrial 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt reducing activity and plasma membrane lactate dehydrogenase release. These data suggest that soybean-derived PI may be useful as a therapeutic and/or preventive strategy for Alzheimer's disease.