Amyloid β peptides act directly on single neurons

A peptide consisting of residues 25–35 of the amyloid β protein was applied to single neurons while monitoring membrane current by whole cell voltage clamp recording. Within minutes of direct exposure of a neuron to the amyloid β peptide, a paroxysmal increase in neuronal membrane conductance was observed. This conductance does not resemble previously described ionic conductances in terms of its time-dependence, voltage-dependence or sensitivity to changes in extracellular or intracellular ionic constituents. The effect of the amyloid β peptide was not mimicked or blocked by substance P nor was it prevented by low intracellular or extracellular Ca. The increased membrane permeability elicited by the peptides may lead to the neuropathology observed in Alzheimer's disease.