THE IMMUNOREACTIVE PROFILE AT THE N-TERMINAL REGION OF A-BETA-1-39 40BUT NOT A-BETA-1-42 CHANGES WITH TRANSITION FROM MONOMER-DIMER TO FURTHER PEPTIDE AGGREGATES/

Using site-specific antibodies, we assessed the effect of aggregation of various length forms of A beta on the immunoreactive profile of the peptides. All of the antibodies tested reacted with monomeric/dimeric forms of A beta 1-42 and its further aggregates. However, antibodies directed against the 1-24 region of A beta reacted weakly or not at al l with A beta 1-39/40 monomers or dimers, but immunoreactivity was enh anced substantially following peptide incubation and aggregation. Thes e results suggest that the conformation of the N-terminal region of mo nomeric and dimeric A beta 1-39/40 is different from that of aggregate d forms, whereas the longer AP 1-42 does not significantly change its N-terminal conformation during beta-sheet fibril formation. These immu nochemical results are consistent with previous structural data, and h elp to explain the differential effects of A beta 1-39/40 and 1-42 on fibril formation in brain.