Inhibition of LTP in vivo by beta-amyloid peptide in different conformational states

We have investigated changes in the morphological structure of Abeta1-40 during different incubation time periods at 37 degrees C ranging from 1 h to 7 days using Thioflavin T, Congo red binding and electron microscopy. We found distinctive changes in Abeta assembly demonstrating the formation of beta pleated sheets following 7-day incubation. Here we demonstrate that samples of the same Abeta1-40 peptide that are morphologically distinct can both attenuate hippocampal long-term potentiation (LTP) in the CA1 in vivo. The peptides were applied via intracerebroventricular injection and the effects on synaptic transmission, post-tetanic potentiation (PTP) and LTP were observed. The effects of Abeta1-40 that had either been freshly solubilized (FS-Abeta) or incubated at 37 degrees C for 7 days (7D-Abeta) were examined. FS-Abeta and 7D-Abeta peptide were both found to significantly attenuate LTP, although the assembly states of these peptides appeared to be completely different. Paired pulse facilitation (PPF) with an inter-stimulus interval of 50 ms was also monitored prior to, following peptide injection and 60 min following LTP induction. 7D-Abeta caused an increase in PPF prior to LTP induction and also depressed PTP. Our data demonstrate that, while both forms of the peptide can attenuate LTP, the fibrillar form of the peptide may also influence transmitter release.