BLOCK OF LTP IN RAT HIPPOCAMPUS IN-VIVO BY BETA-AMYLOID PRECURSOR PROTEIN-FRAGMENTS

THE effects of beta-amyloid precursor protein (beta-APP) fragments on plasticity of glutamtatergic synaptic transmission were examined in th e hippocampus of urethane anaesthetized rats. I.c.v. injection of beta -amyloid (A beta) 1-40 and 1-42 and the C-terminal fragment CT105 grea tly shortened the duration of high frequency stimulation-induced long- term potentiation (LTP) of held excitatory postsynaptic potentials in the CA1 area. Whereas in vehicle injected animals LTP was stable over a 5 h recording period, doses of these peptides (A beta 1-40, 0.4 and 3.5 nmol; A beta 1-42, 0.01 nmol; CT105, 0.05 nmol) which did not affe ct baseline synaptic transmission abolished LTP within 3-5 h. The redu ced duration of this form of synaptic plasticity may contribute to the cognitive deficits in Alzheimer's disease.