Impairment of hippocampal long-term potentiation by Alzheimer amyloid beta-peptides

Although it is generally believed that amyloid beta (A beta) peptides contr ibute to the pathogenesis of Alzheimer's disease, the precise role of these peptides in the development of memory loss of Alzheimer's disease, has not been fully understood. The present study examined the effect of several sy nthetic A beta peptides on long-term potentiation (LTP), a cellular model o f learning and memory, in rat hippocampal slices. Brief perfusion of slices with low concentrations (200 nM or 1 mu M) of A beta(1-42), A beta(1-40), or their active fragment A beta(25-35) significantly inhibited LTP inductio n without affecting the basal synaptic transmission and posttetanic potenti ation in the dentate medial perforant path. A similar effect of A beta(25-3 5),, was also observed in the Schaffer colleteral-CAl pathway. When compari ng actions of several A beta variants derived from A beta(25-35), the N-ter minal sequence of A beta(25-35) was found necessary for inhibiting LTP, In addition, A beta variants lacking neurotoxic action and aggregating propert y were also able to block LTP, suggesting that this effect was neurotoxicit y independent. Our findings demonstrated that subneurotoxic concentrations of A beta peptides could strongly suppress long-term synaptic plasticity in the hippocampus. Such an effect might underlie the memory deficits seen in Alzheimer's disease before neuronal cell loss. J. Neurosci. Res. 60:65-72, 2000. (C) 2000 Wiley-Liss, Inc.