You might recall that RAGE, the receptor for advanced glycation end-products (AGEs), is thought to have a role in Alzheimer's disease - it's a mechanism that can explain some of the diabetes-like risk factors noted for the development of this condition, making it look a lot like a lifestyle disease. Here, researchers look at RAGE vaccines as a possible Alzheimer's therapy: "In Alzheimer's, the amyloid protein can accumulate in the brain instead of being eliminated by the body's natural defenses, nestling between the neurons and forming impassable plaques. Amyloid and the way it gets there could be targets for a new vaccine. ... RAGE, or receptor for advanced glycation endproducts, proteins bind to amyloid and transport it into the brain ... Research has shown that RAGE may also contribute to the inflammation and damage that amyloid causes to the brain's nerve cells. [Scientists are] researching a vaccine that targets RAGE and amyloid by using the body's own immune system to protect against their over-production and eventual build-up. ... Unfortunately, all of the vaccines for Alzheimer's that have been through clinical trials have failed. Part of the reason why could be that they're just not comprehensive enough. Most only target amyloid. Our hope is that by taking a more encompassing approach, we will be more effective. So far, that's exactly what we're seeing in our experiments. ... Early results have shown improved cognition and memory in animal models of Alzheimer's ... We need to move on to larger animal studies. We have a lot we still don't know about the vaccine itself. For example, we know that amyloid and RAGE bind together, but we don't know why the binding creates such a stable complex. We have these end points, but we still don't know some of the basic science that needs to be known so that we can push ahead."