title: An abnormality of plasma amyloid protein precursor in Alzheimer's disease.
abstract: beta A4 amyloid deposition in the brain, which is characteristic of Alzheimer's disease (AD), may result from either overexpression of the amyloid protein precursor (APP) or failure of APP to be correctly processed. A blood marker reflecting this abnormal metabolism would be of diagnostic value and would provide a means of monitoring the efficacy of therapeutic interventions. We analyzed immunoblots of plasma APP enriched by heparin-Sepharose chromatography from patients with moderate to severe AD dementia (n = 34) and control subjects (n = 77) and found an approximately 50% increase in the proportion of 130-kd APP species in patients with AD (p less than 0.001), no difference in the 110-kd form, a 15 to 30% decrease in the 65-kd form (p less than 0.001), and a 20 to 35% decrease in the proportion of 42-kd APP (p less than 0.001). These species of APP were soluble, lacked the carboxyl terminus, and the 110- and 42-kd species were shown to be consistent with degradation products derived from the 130-kd species. A comparison of levels of 130-kd plasma APP from moderately to severely demented patients with AD and control subjects distinguished the two groups with a specificity of 87.0% and a sensitivity of 79.4%.
authors.affiliation: Department of Pathology, University of Melbourne, Australia.
authors.forename: A I
authors.initials: AI
authors.lastname: Bush
authors.forename: S
authors.initials: S
authors.lastname: Whyte
authors.forename: L D
authors.initials: LD
authors.lastname: Thomas
authors.forename: T G
authors.initials: TG
authors.lastname: Williamson
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Tiggelen
authors.forename: J
authors.initials: J
authors.lastname: Currie
authors.forename: D H
authors.initials: DH
authors.lastname: Small
authors.forename: R D
authors.initials: RD
authors.lastname: Moir
authors.forename: Q X
authors.initials: QX
authors.lastname: Li
authors.forename: B
authors.initials: B
authors.lastname: Rumble
mesh_terms: D000544:Alzheimer Disease / Q000097:blood*; D016564:Amyloid beta-Protein Precursor / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D006801:Humans; D008875:Middle Aged; D008970:Molecular Weight; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D000911:Antibodies, Monoclonal; D012697:Serine Endopeptidases