From the neuritic plaques and vascular walls of the brains of patients with Alzheimer disease, we have purified and quantified an A beta peptide which starts at residue 3Glu in the form of pyroglutamyl (A beta3pE). The N-terminally truncated A beta3pE comprised 51% of the A beta in the neuritic plaques. This was followed by 30% starting at position 1Asp which included 20% in the isomerized form (IsoAsp). In contrast, the vascular amyloid only contained an average of 11% in the form of A beta3pE with the major component starting at residue 1Asp (69%), which included only 6% in the form of IsoAsp. The presence of A beta3pE has important structural consequences since it is more hydrophobic than other forms of A beta, thus increasing the insolubility of A beta. In addition, A beta3pE, with its blocked N-terminus to the action of common aminopeptidases, may result in the profuse accumulation of A beta in the neuritic plaques of Alzheimer disease.
