Effect of LY450139 on Aβ secretion in SH-SY5Y cells. A. In SH-SY5Y APPwt cells (closed circles), LY450139 produced a biphasic response with Aβ40-levels increasing in response to low concentrations of inhibitor, reaching 60% above baseline at 3 nM, while at higher concentrations Aβ40 levels started to decrease with an approximate IC50 of 90 nM. In APPswe-transfected SH-SY5Y cells (open circles), LY450139 produced a monophasic concentration-dependent inhibition of Aβ40-secretion with an IC50 of 18 nM. B. LY450139 (3 nM) increased Aβ42 levels by 70% as compared to control in SH-SY5Y APPwt cells, whereas Aβ42 levels in APPswe cells were not affected.