The amyloid precursor protein of Alzheimer's disease is released by human platelets.
Western blots of normal human platelets, employing a monoclonal antibody raised against the full-length amyloid precursor protein of Alzheimer's disease (APP695), revealed major bands of 100-110 and 120-130 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 response to stimulation revealed that platelets release APP during degranulation. The function of platelet APP is yet to be determined, but the present studies suggest a role in regulation of the coagulation cascade or in platelet aggregation.
Bush
A I
AI
Department of Pathology, University of Melbourne, Australia.
Martins
R N
RN
Rumble
B
B
Moir
R
R
Fuller
S
S
Milward
E
E
Currie
J
J
Ames
D
D
Weidemann
A
A
Fischer
P
P
D000544:Alzheimer Disease / Q000097:blood*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000097:blood* / Q000302:isolation & purification; D016564:Amyloid beta-Protein Precursor; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000097:blood; D011498:Protein Precursors / Q000097:blood* / Q000302:isolation & purification; D012016:Reference Values
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D011480:Protease Inhibitors; D011498:Protein Precursors; D011464:Epoprostenol