Alzheimer beta-amyloid blocks epileptiform activity in hippocampal neurons.

Several studies showed that hippocampal neurons respond with an increase in synaptic transmission after chronic blockade of GABA(A) receptors with bicuculline, a neuroplastic phenomenon likely associated to epileptiform states. Here, we tested the effect of Abeta(1-40) oligomers/aggregates, believed to be involved in Alzheimer's Disease (AD) genesis, on this type of synaptic plasticity. In the presence of bicuculline, the frequency of miniature currents increased from 1.2+/-0.4 Hz to 3.1+/-0.6 Hz (n=6, p<0.05). Similarly, current amplitude increased from 45+/-3 pA to 81+/-11 pA (n=5, p<0.05). These effects were completely inhibited in the presence of Abeta(1-40) aggregates. Data suggest that Abeta aggregates exert their influence principally by blocking synaptic transmission and altering the transcriptional pathway associated with CREB-p. In conclusion, neurons exposed to aggregated Abeta(1-40) showed a reduced level of neuronal plasticity and this suggests that they might be acting as anti-epileptiform modulators.