title: beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease.
abstract: Reinvestigation of the chemical structure of beta-amyloid peptide (A beta) deposits in the vascular tissue of Alzheimer disease brains revealed that the 42-residue form A beta-(1-42), rather than the more soluble A beta-(1-40) form, is the predominant peptide. Following removal of the surrounding tissue with SDS and collagenase, A beta was solubilized in formic acid and purified by Superose 12 chromatography. Peptides generated by enzymatic and chemical digestion of the A beta were purified by HPLC and characterized by amino acid analysis, sequence analysis, and mass spectrometry. In the leptomeningeal vessels, the average ratio of A beta-(1-42)/A beta-(1-40) was 58:42, whereas in the parenchymal vessels this ratio was 75:25. Interestingly, vascular A beta contains considerably less isomerized and racemized aspartyl residues than does neuritic plaque A beta, suggesting that the vascular amyloid is "younger." The discrete nature of the bands and spherical deposits of A beta associated with arterioles and capillaries, respectively, suggests that this amyloid arises from the vascular tissue itself. Increasing A beta deposition appears to lead to the distortion and occlusion of capillaries, which may contribute significantly to the pathology of Alzheimer disease.
authors.affiliation: Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201.
authors.forename: A E
authors.initials: AE
authors.lastname: Roher
authors.forename: J D
authors.initials: JD
authors.lastname: Lowenson
authors.forename: S
authors.initials: S
authors.lastname: Clarke
authors.forename: A S
authors.initials: AS
authors.lastname: Woods
authors.forename: R J
authors.initials: RJ
authors.lastname: Cotter
authors.forename: E
authors.initials: E
authors.lastname: Gowing
authors.forename: M J
authors.initials: MJ
authors.lastname: Ball
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001812:Blood-Brain Barrier; D001923:Brain Chemistry; D002560:Cerebrovascular Circulation; D006801:Humans; D013058:Mass Spectrometry; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D009842:Oligopeptides