title: Altered amyloid protein processing in platelets of patients with Alzheimer disease.
abstract: BACKGROUND
  beta-Amyloid peptide, the core component of neuritic plaques in brain areas in patients with Alzheimer disease (AD), is 1 cleavage product of the beta-amyloid precursor protein (APP) in neurons and platelets. Alternate cleavage products of intact 140- to 150-kd APPs in platelets include nonamyloidogenic 120- to 130-kd and 110-kd isoforms. The possible differential significance of these 2 isoforms, structurally similar to protease nexin II, is unknown.
  
  
  OBJECTIVE
  To determine whether the ratio of the 120- to 130-kd APP isoform to the 110-kd APP isoform as processed in platelets correlates with the presence of AD and/or the apolipoprotein E4 (ApoE4) allele, which is a major risk factor for AD.
  
  
  METHODS
  The Alzheimer Disease Center at The University of Texas Southwestern Medical Center at Dallas.
  
  
  METHODS
  The APP isoforms were quantitated with the use of 2 different Western blot detection methods in platelets from 15 patients with AD and 19 control subjects in whom genotyping of apolipoprotein E was performed.
  
  
  RESULTS
  The mean ratio of the 120- to 130-kd APP isoform to the 110-kd APP isoform in the patients with AD was significantly lower than that of the control subjects (5.98 vs 7.64; P = .03 [method 1] and 5.98 vs 7.92; P = .01 [method 2]) after adjusting for age and the increased incidence of ApoE4 in patients with AD. The lower APP ratios were also associated with increased age and with the presence of an ApoE4 allele.
  
  
  CONCLUSIONS
  The APP processing in platelets of patients with AD is different from that of control subjects. This difference, largely caused by factors other than the ApoE4 genotype, may reflect chronic platelet activation in patients with AD. The use of these data to estimate "AD risk," by using the APP isoform ratio, indicates an odds ratio of 1.75, suggesting possible utility as an adjunct in the diagnosis of AD. Moreover, these findings may relate to analogous alterations in APP processing that may occur in brain areas affected by AD.
authors.affiliation: Department of Neurology, University of Texas Southwestern Medical Center at Dallas, USA.
authors.forename: R N
authors.initials: RN
authors.lastname: Rosenberg
authors.forename: F
authors.initials: F
authors.lastname: Baskin
authors.forename: J A
authors.initials: JA
authors.lastname: Fosmire
authors.forename: R
authors.initials: R
authors.lastname: Risser
authors.forename: P
authors.initials: P
authors.lastname: Adams
authors.forename: D
authors.initials: D
authors.lastname: Svetlik
authors.forename: L S
authors.initials: LS
authors.lastname: Honig
authors.forename: C M
authors.initials: CM
authors.lastname: Cullum
authors.forename: M F
authors.initials: MF
authors.lastname: Weiner
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000097:blood*; D016229:Amyloid beta-Peptides / Q000031:analogs & derivatives / Q000097:blood*; D001057:Apolipoproteins E / Q000235:genetics; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E