Background: The beta-site APP cleaving enzyme-1 (BACE1) is a major target for drug design in Alzheimera??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 Abeta 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 Abeta production were measured by enzyme-linked immunosorbent assay and western blotting. Results: Treatment of cortical neurons with heparin inhibited Abeta secretion. However, this effect was not mediated via inhibition of BACE1. Conclusions: Heparin or other glycosaminoglycans may have value for the treatment of Alzheimera??s disease. However, the data do not support the view that a heparin-induced decrease in Abeta secretion is due to inhibition of BACE1.