Amyloid-beta1-42 reduces neuronal excitability in mouse dentate gyrus

Amyloid-β (Aβ) is causally implicated in Alzheimer's disease and neuroplasticity failure has acquired validity as a possible mechanism of early AD pathogenesis. We have previously demonstrated that oligomeric Aβ 1-42 inhibits LTP in the dentate gyrus of rat hippocampal slices. We now show, using whole cell recordings in hippocampal granule cells, that oligomeric Aβ1-42 decreases neuronal excitability. In particular, Aβ1-42 application was associated with a decrease in the number of action potentials fired in response to current injection, and with an increase in the amplitude of the afterhyperpolarization. Reduced excitability may underlie the Aβ-mediated impairment in neuroplasticity, and ultimately may contribute to the memory loss in Alzheimer disease.