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 least two secretory pathways. One generates the A beta peptide and the other a N-terminally truncated A beta fragment termed p3 that is considered non-amyloidogenic. However, direct evidence is missing. We have undertaken to synthesize and purify p3. Pure p3 polymerizes in vitro, forming a lattice with an ultrastructure distinct from the linear fibrils of A beta. In contrast to amyloid, polymerized p3 does not bind thioflavine T. It is therefore concluded that amino acids in the N-terminal part of the A beta molecule are required for formation of typical amyloid fibrils and that the metabolic pathway generating p3 probably is non-amyloidogenic