title: Comparative analysis of human and Dutch-type Alzheimer beta-amyloid peptides by infrared spectroscopy and circular dichroism.
abstract: The 42 amino acid beta A4 peptide is the major constituent of the senile plaques, one of the hallmark neuropathological lesions of Alzheimer's disease. While C-terminally truncated variants were shown to be present in normal body fluids, a single Glu-->Gln change in the 39 amino acid form of beta A4 results in accelerated fibril formation in the brains of patients with Dutch-type hereditary cerebral hemorrhage with amyloidosis. In this study we used Fourier-transform infrared and circular dichroism spectroscopies on synthetic peptides to demonstrate that this mutation results in altered secondary structure in membrane mimicking solvents, characterized by a considerably higher beta-structure content for the mutant peptide. Moreover, extreme high and low pH were less effective in eliminating the beta-conformation for the Dutch-variant than for the normal human sequence.
authors.affiliation: Institute for Biodiagnostics, National Research Council Canada, Winnipeg.
authors.forename: H
authors.initials: H
authors.lastname: Fabian
authors.forename: G I
authors.initials: GI
authors.lastname: Szendrei
authors.forename: H H
authors.initials: HH
authors.lastname: Mantsch
authors.forename: L
authors.initials: L
authors.lastname: Otvos
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000686:Amyloidosis / Q000150:complications / Q000235:genetics / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000235:genetics / Q000473:pathology*; D002942:Circular Dichroism; D005583:Fourier Analysis; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D009426:Netherlands; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D012377:Rodentia; D017386:Sequence Homology, Amino Acid; D013055:Spectrophotometry, Infrared
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides