Effect of Heparin on APP Metabolism and Aβ Production in Cortical Neurons

Background: The â-site APP cleaving enzyme 1 (BACE1) is a major target for drug design in Alzheimer’s disease. BACE1 binds strongly to heparin and other glycosaminoglycans, and there is evidence that the enzyme may interact with proteoglycans in vivo. Several studies suggest that heparin or heparan sulfate analogues may have value as therapeutic agents for the treatment of AD. Objective: To determine whether heparin can inhibit Aâ production in cortical neurons by inhibiting BACE1. Methods: Cortical neurons from APP (SW) Tg2576 mice were incubated with heparin and the amount of APP processing and Aâ production were measured by enzyme-linked immunosorbent assay and Western blotting. Results: Treatment of cortical neurons with heparin inhibited Aâ secretion. However, this effect was not mediated via inhibition of BACE1. Conclusions: Heparin or other glycosaminoglycans may have value for the treatment of Alzheimer’s disease. However, the data do not support the view that a heparin-induced decrease in Aâ secretion is due to inhibition of BACE1.