Altered amyloid protein processing in platelets of patients with Alzheimer disease
R. N. Rosenberg, F. Baskin, J. A. Fosmire, R. Risser, P. Adams, D. Svetlik, L. S. Honig, C. M. Cullum and M. F. Weiner
Department of Neurology, University of Texas Southwestern Medical Center at Dallas, USA.
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. SETTING: 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.
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