I am driven to find a cure for Alzheimer’s disease

Karen Hsiao Ashe has devoted her life to finding a cure for Alzheimer’s disease. Her peers regard her as one of the world’s top researchers of the disease.

Karen Ashe
“Research is sort of like a baseball game. Not much happens for a while, and then someone hits a home run.” Karen Hsiao Ashe, Professor Click to tweet

Among her discoveries, she found that clumps of a tangled-up protein found in the brains of Alzheimer’s patients don’t cause the disease. But that particular brain protein, known as tau, does play a key role. The tangles are clumps of an abnormal form of the protein.

Ashe’s research revealed that a key event in the development of memory loss in mice happens when an enzyme called caspase-2 splits the normal tau protein in two. This produces a fragment of tau that goes on to interfere with normal brain functioning. Keeping the enzyme from splitting tau, she showed, helps mice recover memory capacity.

Ashe now hopes to find a drug that will do the same in human patients. One University colleague—Michael Walters—and his team are screening chemicals, looking for this kind of therapeutic potential. If Ashe can align all the necessary public and private resources to develop—and win FDA approval for—a drug to inhibit caspase-2 safely and effectively in humans, she says it could be ready to market in about 10 years.

Could stopping one enzyme also stop Alzheimer’s disease?


How does this tau fragment cause so much trouble?

Neurons have knoblike swellings called spines. Their outer surfaces are dotted with antennae-like molecules that receive signals from other neurons.

The normal, intact tau protein is not found in large amounts in the spines, but the tau fragment leads more tau proteins to stray into the spines, where they become chemically modified.

The modified tau protein causes the disruption and loss of antennae. Now, signals from other neurons “fall on deaf ears,” and the affected neurons eventually die.

“With the tau project, we’re able to reverse some existing memory problems. In a few years, we might be able to take someone who’s beginning to lose their memory, give them a drug, and have their memory function return to normal.” Karen Hsiao Ashe, Professor Click to tweet