The role of the blood-brain barrier (BBB) in Alzheimer’s disease (AD) is poorly understood. Long considered a passive barrier, the BBB is increasingly appreciated as an active regulator of what enters the brain. We recently discovered that the BBB unexpectedly transports many essential blood proteins into the brain—a process disrupted early in AD. With our new proteomics techniques, we will first create a comprehensive map of blood proteins that cross the BBB under healthy conditions and how this fails in AD. This will allow us to pinpoint how the loss of typical transport contributes to AD and discover new BBB “entry receptors” that can be harnessed to deliver urgently needed brain-permeable drugs.
