Glutamate Exacerbates Amyloid β1 − 42-Induced Impairment of Long-Term Potentiation in Rat Hippocampal Slices

Amyloid beta (A beta) is the principal constituent of senile plaques in Alzheimer's disease patients. We investigated whether A beta and glutamate affect long-term potentiation (LTP) in rat hippocampal slices. Pretreatment with 1 microM A beta1-42 alone for 3 h slightly inhibited LTP; however, the potentiation was maintained for 60 min. Although the impairment was not observed by pretreatment with 30 microM glutamate alone for 3 h, pretreatment with A beta1-42 and glutamate impaired LTP significantly. These results raise the possibility that neurotoxicity of A beta is exacerbated by the enhancement of susceptibility to excitatory amino acids.