Electrophysiological effects of 25-35 amyloid-beta-protein on guinea-pig lateral septal neurons.

The amyloid-beta-protein (A beta P) is the major component of the amyloid deposition which characterizes Alzheimer's disease. We have investigated the effects of 25-35 A beta P, the biologically active part of A beta P, on 35 lateral septal neurons in slices of guinea-pig brain during intracellular recording. Bath application of 25-35 A beta P (10(-6) M) caused transient or long-lasting membrane depolarizations in 15 neurons. These effects were not obtained with a 25-35 A beta P peptide synthetized at random. In 7 other neurons, in control medium or in presence of tetrodotoxin, 25-35 A beta P increased the amplitude of excitatory responses produced by local iontophoretic applications of glutamate and NMDA. The data demonstrate for the first time the excitatory effects of 25-35 A beta P on central neurons, effects which may be involved in the mechanisms of neuronal death in Alzheimer's disease.