THE JOURNAL OF BIOLOCK!AL CHEMEXRY 0 1990 by The American Society for Biochemistry

and Molecular Biology, Inc.

Vol. 265, No. 26, Issue of September 15, pp. 15977-15963,199O Printed in U.S.A.

The Amyloid Precursor Human Platelets*

Protein of Alzheimer’s

Disease Is Released by
(Received for publication, March 22, 1990)

Ashley I. Bush$Oll, Ralph N. Martins& Baden MilwardS, Jon CurrieB, David Amesn, Andreas Konrad Beyreuther 11,and Colin L. Masters$$**

Rumble$, Robert MoirS, Stephanie Fuller+, Elizabeth Weidemannll , Peter Fischer 11,Gerd Multhaup 11,
Research Institute, Royal Park Hospital, Royal Melbourne HospitaZ, Victoria 3050, Heidelberg, Federal Republic of Germany

From the $Department of Pathology, University of Melbourne, the §Mental Health Parkuille 3052, Austra&a, the llDepartment of Psychiatry, University of Melbourne, Australia, and the 11 Center for Molecular Biology, University of Heidelberg, D-6900

Western blots of normal human platelets, employing a monoclonal antibody raised against the full-length amyloid precursor protein of Alzheimer’s disease (APPssS), revealed major bands of 100-110 and 120130 kDa in both cytosolic, membrane, and released fractions. These species were similar in size to forms seen in brain preparations and in plasma. There was no difference in Western blots of platelet preparations from Alzheimer patients compared with controls. Purified platelet amyloid precursor proteins were sequenced and shown to be amino terminally homogeneous. Immunohistochemistry localized the antigen to the platelet and megakaryocyte and demonstrated weak immunostaining of some lymphocytes. Immunoprecipitation of material released from platelets demonstrated that sedimentable full-length APP with the carboxyl-terminal epitope, and soluble APP lacking the carboxyl-terminal epitope, may exist in the circulation. Western blots and carboxyl-terminal and amino-terminal APP radioimmunoassay of material released by platelets in