Intact Alzheimer amyloid precursor protein (APP) is present in platelet membranes and is encoded by platelet mRNA.
Using antibodies directed against N-terminal and C-terminal epitopes we have immunologically detected APP species in the membrane and saline-soluble fractions of unstimulated platelets, and in the conditioned medium of thrombin-stimulated platelets. These studies demonstrate an intact 140 kD membrane-associated form of APP that is released on degranulation. Evidence that platelets synthesize at least one form of APP (APP751) was obtained by enzymatic amplification of specific mRNA using Polymerase Chain Reaction (PCR) and direct sequence analysis of PCR product. Processing of APP for release may occur via successive C-terminal truncations, and/or by the release and proteolysis of an intact membrane associated form. An intact form of APP in platelets provides a circulating substrate upon which proteases from many tissues may act to produce beta protein (AB) during pathologic conditions.
Department of Pathology, State University of New York, Stony Brook.
J E
JE
Gardella
J
J
Ghiso
G A
GA
Gorgone
D
D
Marratta
A P
AP
Kaplan
B
B
Frangione
P D
PD
Gorevic
D000544:Alzheimer Disease / Q000235:genetics* / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000276:immunology; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies / Q000276:immunology; D001483:Base Sequence; D001792:Blood Platelets / Q000737:chemistry* / Q000187:drug effects; D004247:DNA / Q000737:chemistry; D010450:Endopeptidases / Q000494:pharmacology; D000939:Epitopes; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000235:genetics* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis*; D013917:Thrombin / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D000939:Epitopes; D011498:Protein Precursors; D012333:RNA, Messenger; D004247:DNA; D010450:Endopeptidases; D013917:Thrombin