资源环境科技发展态势分析平台

beta-amyloid (A beta)-dependent neuronal hyperactivity is believed to contribute to the circuit dysfunction that characterizes the early stages of Alzheimer's disease (AD). Although experimental evidence in support of this hypothesis continues to accrue, the underlying pathological mechanisms are not well understood. In this experiment, we used mouse models of A beta-amyloidosis to show that hyperactivation is initiated by the suppression of glutamate reuptake. Hyperactivity occurred in neurons with preexisting baseline activity, whereas inactive neurons were generally resistant to A beta-mediated hyperactivation. A beta-containing AD brain extracts and purified A beta dimers were able to sustain this vicious cycle. Our findings suggest a cellular mechanism of A beta-dependent neuronal dysfunction that can be active before plaque formation.