Differential processing and secretion of Aβ peptides and sAPPα in human platelets is regulated by thrombin and prostaglandine 2

Metabolic and functional studies of the amyloid precursor protein (APP) in platelets have advanced our understanding of Alzheimer's disease (AD). Here we report that human platelets contain Aβ peptides, process and secrete them constitutively. Platelets generate formerly unkown Aβ-species by differential processing of APP. Release of Aβ peptides were also increased by platelet activation with thrombin, indicating the existence of a regulated exocytotic pathway. We showed that Aβ-levels, Aβ-processing patterns and Aβ-release kinetics were regulated by thrombin. In controls, release of Aβ peptide species (Aβ 1-40/42 and 1-37/38/39/) continued for more than 4 h, while thrombin activated cells ceased secretion after 1 h at large. Treatment of platelets with prostaglandine 2 slowed this process down. Intracellular Aβ peptide concentrations decreased steadily until no peptides could be detected after 20 h (control) or after 4 h (thrombin) in cultured platelets.