Aβ42 did not alter insulin-stimulated Akt signaling but moderately suppressed basal Akt activation.<h4>Conclusions</h4>These findings suggest that Aβ40 acutely impairs insulin signal transduction in BBB endothelial cells, supporting a model in which vascular Aβ exposure contributes directly to the early development of brain insulin resistance in AD. The gene discussed is INS; the disease is Alzheimer disease.