Isolation, chemical characterization, and quantitation of A beta 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 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.
Kuo
Y M
YM
Haldeman laboratory for Alzheimer's Disease Research, Sun Health Research Institute, Sun City, Arizona 85351, USA.
Emmerling
M R
MR
Woods
A S
AS
Cotter
R J
RJ
Roher
A E
AE
D000544:Alzheimer Disease / Q000473:pathology*; D000595:Amino Acid Sequence; D000626:Aminopeptidases; D000682:Amyloid / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001808:Blood Vessels / Q000737:chemistry; D001921:Brain / Q000473:pathology*; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013058:Mass Spectrometry; D016501:Neurites / Q000473:pathology*; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification; D014357:Trypsin
D000682:Amyloid; D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D000626:Aminopeptidases; D014357:Trypsin