title: Alzheimer's disease and control brain contain soluble derivatives of the amyloid protein precursor that end within the beta amyloid protein region.
abstract: The 39-43 amino acid beta amyloid protein (A beta) that deposits as amyloid in the brains of patients with Alzheimer's disease (AD) is encoded as an internal sequence within a larger membrane-associated protein known as the amyloid protein precursor (APP). In cultured cells, the APP is normally cleaved within the A beta to generate a large secreted derivative and a small membrane-associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire A beta. Our study was designed to determine whether the soluble APP derivatives in human brain end within the A beta as described in cell culture or whether AD brain produces potentially amyloidogenic soluble derivatives that contain the entire A beta. We find that both AD and control brain contain nonamyloidogenic soluble derivatives that end at position 15 of the A beta. We have been unable to detect any soluble derivatives that contain the entire A beta in either the AD or control brain.
authors.affiliation: Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: J M
authors.initials: JM
authors.lastname: Pasternack
authors.forename: M R
authors.initials: MR
authors.lastname: Palmert
authors.forename: M
authors.initials: M
authors.lastname: Usiak
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Zurcher-Neely
authors.forename: P A
authors.initials: PA
authors.lastname: Gonzalez-De Whitt
authors.forename: M B
authors.initials: MB
authors.lastname: Fairbanks
authors.forename: T
authors.initials: T
authors.lastname: Cheung
authors.forename: D
authors.initials: D
authors.lastname: Blades
authors.forename: R L
authors.initials: RL
authors.lastname: Heinrikson
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D001923:Brain Chemistry; D003488:Cyanogen Bromide; D006801:Humans; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry
chemical_list: D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D003488:Cyanogen Bromide