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.