We previously reported that pathophysiological concentrations of amyloid beta protein (Abeta25-35, 0.1-10 nM) directly inhibited type II phosphatidylinositol 4-kinase (PI4KII) activity in neuronal plasma membranes, which resulted in the enhanced glutamate neurotoxicity. In the present study, we examined the effects of Abeta fragments, Abeta20-29 and Abeta31-35, on the 10 nM Abeta25-35- or Abeta1-42-induced inhibition of PI4KII activity. Both of the peptide fragments recovered the inhibition of rat brain plasma membrane PI4KII activity over the concentration range of 0.1-5 nM. Such protection by the Abeta fragments was observed in the 10 nM Abeta25-35-induced inhibition of recombinant human PI4KII, suggesting that these Abeta fragments blocked the inhibition on PI4KII molecule. The Abeta25-35-induced enhancement of glutamate neurotoxicity was also completely inhibited in the presence of these fragments. Thus, Abeta20-29 and Abeta31-35 ameliorated the Abeta-enhanced glutamate neurotoxicity probably through attenuation of Abeta-induced inhibition of PI4KII activity.