THE METABOLIC PATHWAY GENERATING P3, AN A-BETA-PEPTIDE FRAGMENT, IS PROBABLY NON-AMYLOIDOGENIC

The Alzheimer A beta amyloid precursor protein is metabolized by at le ast two secretory pathways. One generates the A beta peptide and the o ther a N-terminally truncated A beta fragment termed p3 that is consid ered non-amyloidogenic. However, direct evidence is missing. We have u ndertaken to synthesize and purify p3. Pure p3 polymerizes in vitro, f orming a lattice with an ultrastructure distinct from the linear fibri ls of A beta. In contrast to amyloid, polymerized p3 does not bind thi oflavine T. It is therefore concluded that amino acids in the N-termin al part of the A beta molecule are required for formation of typical a myloid fibrils and that the metabolic pathway generating p3 probably i s non-amyloidogenic. (C) 1994 Academic Press, Inc.