The Ashe Lab

“Research is sort of like a baseball game. Not much happens for a while and then someone hits a homerun.”
~Karen Hsiao Ashe, MD, PhD, Founding Director, N. Bud Grossman Center for Memory Research and Care

The N. Bud Grossman Center for Memory Research and Care continually aims to expand high-impact research that moves the needle toward an eventual cure. The Ashe Lab team examines key proteins and processes that they believe underlie Alzheimer’s, while building research partnerships to expedite mouse models and drug development. These collaborations are paving the way for effective treatment and prevention strategies in humans.

Initial Research Question: Are neurofibrillary tangles the cause of Alzheimer’s disease and neurodegeneration?
Answer: No. Over the last decade, Karen Ashe and her team have found that tangles are not the cause of Alzheimer’s, but rather a sign of the disease. Tau* is likely a culprit. Today, the main focus of the Ashe lab’s research is developing a drug to stop the damage caused by tau*.


Stopping Tau*

“With the tau project, we’re able to reverse existing problems in mice. So we might be able to take someone who’s beginning to lose their memory, give them something, and have their memory function return to normal.”
~Karen Hsiao Ashe, MD, PhD

In 2016, Karen Ashe and her research team had their most productive year yet in terms of understanding the role of tau* in Alzheimer’s, and finding ways to prevent its impact. This work was launched years ago by donor and National Institutes of Health support and it was recently published in Nature Medicine (see below). This research path shows immense promise and Dr. Ashe recently decided to dedicate the remainder of her research career to developing a tau* drug and devising a test to measure tau* in people.

Over the past year, Ashe and her team have made a significant discovery about how tau* triggers neurodegeneration. They found that after being formed by an enzyme called caspase 2, tau* causes other forms of tau to infiltrate the dendritic spines (or antennae) of neurons and prevents them from carrying out effective communication.

Before taking a new position in Maryland, Dr. Xiaohui Zhao led this tau project to a successful conclusion (see Nature publication below). Of Xiaohui’s tremendous work, Dr. Ashe said, His command of experimental design and technique, leadership, and dedication were second to none. There is no doubt that he was the MVP in this epic project. 

Ashe’s team is now working to identify compounds that protect and restore communication between neurons by preventing tau* from forming. They have built partnerships with colleagues from the University, private donors, and a major pharmaceutical company to achieve this goal. With the help of Dr. Michael Walters and his team at the Institute for Therapeutics Discovery and Development (ITDD), they are now screening these chemicals to determine if any of them block the enzyme that generates tau*. Their next big steps will involve testing the most promising compounds in animal models and potentially moving these compounds to human clinical trials.


New Ashe Lab publication in Nature Medicine

Ashe Lab researchers identified a potential target for treating Alzheimer’s disease, which reversed memory loss in mice. This research marks a significant step forward in the fight against Alzheimer’s disease and memory loss. The research is published in the current issue of Nature Medicine.