Characterization of Alzheimer amyloid precursor protein transcripts in platelets and megakarocytes

Abstract

Immunoblot analyses indicate that the platelet is a reservoir of several Alzheimer amyloid precursor protein (APP) isoforms, including C-terminal reactive species which could potentially serve as the precursor of the amyloid beta protein ( A B ∗ ∗ Husby, G., Araki, S., Benditt, E.P., Benson, M.D., Cohen, A.S., Frangione, B., Glenner, G.G., Natvig, J.B. and Westermark, P., The 1990 guidelines for nomenclature and classification of amyloid and amyloidosis. In J.B. Natvig et al. (Eds.), Amyloid and Amyloidosis 1990, Kluwer, Dordrecht, 1991, pp. 7–11. ) in Alzheimer's disease (AD). Since platelets are known to sequester several plasma proteins from the blood, we employed the polymerase chain reaction (PCR) to amplify reverse transcribed mRNA and detect the 3 major APP transcripts (APP 695,751,770) in platelets and the Dami megakaryocyte cell line. PCR amplification of glycoprotein IIb and HLA-DR mRNA was used to demonstrate that APP transcripts were derived from cells of megakaryocytic lineage, and the results were compared with those obtained from peripheral blood mononuclear cells, human umbilical vein endothelial cells, B lymphocyte and astrocytoma cell lines. The identity of PCR products was confirmed by hybridization with APP specific oligonucleotide probes, and sequencing of amplified segments.