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Membrane-associated forms of the beta A4 amyloid protein precursor of
Alzheimer's disease in human platelet and brain: surface expression on the
activated human platelet
QX Li, MC Berndt, AI Bush, B Rumble, I Mackenzie, A Friedhuber, K Beyreuther and CL Masters
Department of Pathology, University of Melbourne, Parkville, Victoria,
Australia.
The amyloid protein precursor (APP) of Alzheimer's disease (AD) is
abundantly expressed in platelets, where its primary function remains
undetermined. As an integral transmembrane protein, the release of APP from
the membrane may be a critical event in AD. We examined the association of
APP with human platelet membranes using a combination of alkali treatment
and immunoprecipitation of the carboxyl-terminus of APP. Most of the
platelet membrane-associated APP (APPMem) with molecular mass of 100 to 130
kD is removed with alkali treatment and is also truncated at the
carboxyl-terminus. APPMem is present at least in part on the surface of the
platelet. The full-length transmembrane form of APP, as a 140- to 150-kD
minor species, is alkali resistant and is also present on the plasma
membrane. In contrast, most of the APPMem from brain is full-length
(possessing the carboxyl-terminus) with a molecular mass of 105 to 130 kD
and is resistant to alkali treatment. Immunoelectron microscopy shows
platelet APP to be localized to the alpha-granule. Activation of platelets
results in a threefold increase in surface APP detectability. In plasma,
the 130-kD APP-reactive band is increased in AD. We find that in the gray
platelet syndrome, platelets contain reduced amounts of APP, with a
corresponding reduction in plasma APP levels, suggesting that platelets are
the major source of plasma APP. Our studies also identify an interaction of
APP with platelet membranes which differs from that found in the brain, and
raise the possibility of a receptor for APP in platelet membranes.
Quantitative differences in the amounts of APPMem in platelets compared
with brain also indicate regulation of the pathways that determine the
cleavage of APP near its transmembrane domain. These pathways are a
therapeutic target in AD, and may be easily amenable to investigation in
platelets.
Volume 84,
Issue 1,
pp. 133-142,
07/01/1994
Copyright © 1994 by The American Society of Hematology
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