A recent study has linked changes in the vascular system to Alzheimer's disease.

A team of Rockefeller scientists has found that a plasma component normally involved in blood clotting and inflammation may also be part of the problem in some patients. This isn't the first time the condition has been linked to the vascular system. "There's a lot of evidence that exercise, which helps keep your blood vessels healthy and blood flow consistent, can be protective against AD," said researcher Sidney Strickland. "In addition, we know that diseases that compromise the vascular system, like diabetes, put people at higher risk."

Yet it's still not clear precisely how changes in the blood might spur Alzheimer's. The latest study from Strickland's lab offers a clue and a possible path to early diagnosis and new drugs. The plasma protein, called Factor XII, is part of a cascade of enzymes that induces blood coagulation and inflammation. "We speculated that activation of Factor XII by beta-amyloid could play a role in initiating Alzheimer's," said senior author Zu-Lin Chen. "That's not something you can study in humans, so we looked at mouse models of disease to see what happens when Factor XII is knocked down."

To take out Factor XII, the team used a molecule that prevented the gene from making the protein. Normally, AD mice show much greater brain inflammation than healthy mice. However, AD mice whose Factor XII had been knocked down had much less inflammation than untreated AD mice and had brains that were more similar to those of healthy mice. In addition, behavioral studies of AD mice with reduced Factor XII showed that their cognitive function improved. In one test, the mice were introduced to a maze with an escape hole. The animals learn the location of the hole by remembering visual cues around the maze, allowing them to escape through the hole on subsequent visits. Unlike normal mice, AD mice are unable to remember where the hole was located.

Knocking down Factor XII helped: AD mice lacking the protein learned to find their way quicker than the untreated AD mice, although their memory wasn't as good as that of normal mice. These and other findings in the study point to one potential factor in initiating AD, though the researchers caution they may not lead to new drugs anytime soon. The study is published in the journal Blood.