A vicious cycle of β amyloid–dependent neuronal hyperactivation

Β-amyloid (Aβ)-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 Aβ-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 Aβ-mediated hyperactivation. Aβ-containing AD brain extracts and purified Aβ dimers were able to sustain this vicious cycle. Our findings…

• AA
  Alzheimer's Association

  Award: ZEN-18-533290
• BF
  BrightFocus Foundation

  Award: A2013059S
• DF
  Deutsche Forschungsgemeinschaft

  Award: SFB 870
• GH
  Gemeinnützige Hertie-Stiftung
• NI
  National Institutes of Health

  Award: AG046275
• NI
  National Institute on Aging

  Award: AG005134