The Bahrs are not the only ones who feel the promise of Alzheimer’s research. So do the scientists.

“The research has just exploded,” says Suman Jayadev, M.D., UW associate professor of neurology, director of the UW Neurogenetics Clinic and the Arthur Krause Professor for Neurogenetics Research.

This explosion of research is a response to an urgent need to find effective treatments, one codified by a national goal to find a cure for Alzheimer’s disease by 2025.

“In the last 10 years, we’ve made a lot of progress in understanding the genetic risk factors,” says Jayadev, who researches the genetics and basic mechanisms that lead to the accumulation of amyloid plaques and tau protein tangles in the brain — the hallmarks of Alzheimer’s disease.

“We can now look across a person’s genome and find areas that are associated with higher risk for Alzheimer’s disease,” she says. “We can then try to understand what the genes in those regions are doing that leads to Alzheimer’s.”

Jayadev also points out that access to the brain has thwarted Alzheimer’s disease research for a long time. It’s been a big problem. You can’t easily take a brain sample and send it to a lab, as you can with a tumor, unless the donor of the sample is deceased. However, stem cell technology is providing new solutions.

“We can actually grow human brain cells, look at them under the microscope and test their properties,” says Institute for Stem Cell and Regenerative Medicine researcher Jessica Young, Ph.D., UW assistant professor of pathology.

Using induced pluripotent stem cell technology, Young and Jayadev are collecting skin cells from patients with and without Alzheimer’s disease and reprogramming them into human neuronal models. They then use these “brain cells in a dish” to test potential drug compounds.

“These stem cell-derived brain cells will allow us to test new compounds that, potentially, could be active and effective during the early stages of the disease,” says Young.

“What people don’t realize is that Alzheimer’s dementia is actually the late manifestation of a disease that has been going on for decades,” says Tom Grabowski, Jr., M.D., radiologist and director of the UW Medicine Memory & Brain Wellness Center. “Those early periods of the disease are an opportunity for intervention.”

Grabowski, who is also the director of the Integrated Brain Imaging Center, is using imaging — PET scans and MRI technology — to detect toxic protein buildup in the brain before a person displays any symptoms of dementia. This technology could serve as a more reliable diagnostic tool and catch people during a critical window of time when therapy is most likely to succeed.

All of this research — genetic sequencing, stem cell research, MRI imaging — reflects a precision-medicine approach that emphasizes treatment based on an individual’s genetic and molecular profile. This approach is particularly well-suited to Alzheimer’s disease research, since Alzheimer’s, like cancer, is a disease that expresses itself differently in different people. One cure is unlikely; multiple cures, suited to different people, is the goal.

UW Medicine is leading the precision-medicine research approach to Alzheimer’s thanks to a gift from the Ellison Foundation. Having lost family and friends to Alzheimer’s, donors Tom and Sue Ellison decided to become part of the solution. Their gift helped create a “discovery-to-therapy” pipeline at UW Medicine to quickly test new ideas in clinical trials.

The pipeline speeds up the normally slow process of drug development — a priority for researchers and patients alike.

Alzheimer’s is a death sentence. Except when it’s not.

“You can have Alzheimer’s disease and not develop dementia,” says Kristoffer Rhoads, Ph.D., a neuropsychologist at the UW Medicine Memory & Brain Wellness Center. He works with patients on lifestyle and behavioral interventions.

“I’m consistently impressed by the cases of autopsied brains that have a high burden of plaques and tangles, but the person didn’t have significant memory or functional problems,” Rhoads says.

There is a specific term for this phenomenon in the world of Alzheimer’s research: resilience. Imaging research has shown a link between more education and higher levels of resilience, but there is more to it than that.

“Certain lifestyle factors, physical exercise, social engagement and a cognitively active lifestyle — all of these have been shown to favorably affect the course of cognitive aging, and they can change the time that somebody develops memory impairment by a decade or more,” says Grabowski.

Square dancing checks more than one box on the resilience checklist. That’s been a motivating factor for Joe, who has fallen in love with the activity.

“When you’re out there square dancing, you’re communicating with each other. You touch. You hug. You’re moving around. There are over a hundred calls, and you have to respond immediately. It’s really good for the brain, and it’s also very social,” says Joe.

Which brings us back to the brothers’ pact. Before Marty died, he promised Joe that he would donate his brain to science if Joe raised money for Alzheimer’s disease research.

Both brothers upheld their end of the bargain. For 11 years running, Joe has organized Remember to Dance, an annual square dance benefit that raises money for research at UW Medicine’s Alzheimer’s Disease Research Center, where Marty was diagnosed. And Joe shows no signs of slowing down.

“If we could find a cure, it would be so amazing,” he says.

By Eleanor Licata
Photos: Doug Plummer