Rn. Rosenberg et al., ALTERED AMYLOID PROTEIN PROCESSING IN PLATELETS OF PATIENTS WITH ALZHEIMER-DISEASE, Archives of neurology, 54(2), 1997, pp. 139-144
Background: beta-Amyloid peptide, the core component of neuritic plaqu
es in brain areas in patients with Alzheimer disease (AD), is 1 cleava
ge product of the P-amyloid precursor protein (APP) in neurons and pla
telets. Alternate cleavage products of intact 140- to 150-kd APPs in p
latelets include nonamyloidogenic 120- to 130-kd and 110-kd isoforms.
The possible differential significance of these 2 isoforms, structural
ly similar to protease nexin II, is unknown. Objective: To determine w
hether the ratio of the 120- to 130-kd APP isoform to the 110-kd APP i
soform as processed in platelets correlates with the presence of AD an
d/or the apolipoprotein E4 (ApoE4) allele, which is a major risk facto
r for AD. Setting: The Alzheimer Disease Center at The University of T
exas Southwestern Medical Center at Dallas. Methods: The APP isoforms
were quantitated with the use of 2 different Western blot detection me
thods 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 t
he patients with AD was significantly lower than that of the control s
ubjects (5.98 vs 7.64; P = .03 [method 1] and 5.98 vs 7.92; P = .01 [m
ethod 2]) after adjusting for age and the increased incidence of ApoE4
in patients with AD. The lower APP ratios were also associated with i
ncreased age and with the presence of an ApoE4 allele. Conclusions: Th
e APP processing in platelets of patients with AD is different from th
at of control subjects. This difference, largely caused by factors oth
er than the ApoE4 genotype, may reflect chronic platelet activation in
patients with AD. The use of these data to estimate ''AD risk,'' by u
sing the APP isoform ratio, indicates an odds ratio of 1.75, suggestin
g possible utility as an adjunct in the diagnosis of AD. Moreover, the
se findings may relate to analogous alterations in APP processing that
may occur in brain areas affected by AD.