Isolation, chemical characterization, and quantitation of Aβ 3-pyroglutamyl peptide from neuritic plaques and vascular amyloid deposits

From the neuritic plaques and vascular walls of the brains of patients with Alzheimer disease, we have purified and quantified an Aβ peptide which starts at residue 3Glu in the form of pyroglutamyl (Aβ3pE). The N-terminally truncated Aβ3pE comprised 51% of the Aβ 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 Aβ3pE with the major component starting at residue 1Asp (69%), which included only 6% in the form of IsoAsp. The presence of Aβ3pE has important structural consequences since it is more hydrophobic than other forms of Aβ, thus increasing the insolubility of Aβ. In addition, Aβ3pE, with its blocked N-terminus to the action of common aminopeptidases, may result in the profuse accumulation of Aβ in the neuritic plaques of Alzheimer disease.