Recent breakthroughs have revealed a great deal about Alzheimer’s disease, but researchers have yet to paint a complete picture of how genetic risk for the illness causes the brain damage that ultimately leads to memory loss and cognitive decline. A new study from the Keck School of Medicine of USC, just published in the Journal of Experimental Medicine, adds a crucial piece to that puzzle. It documents, in real time, that APOE4, the main susceptibility gene for Alzheimer’s disease, leads to molecular changes in the brain’s blood vessels, which are then followed by changes in the synapses that connect brain cells. The study also suggests potential targets in blood vessels for treatment early in the disease process—before cognitive decline occurs.