UW Medicine researchers close in on treatments for Alzheimer’s

“As children, we were close,” says Joe Bahr about his older brother, Marty. Though their worlds drifted apart as adults, the brothers reconnected when Marty was diagnosed with early-onset Alzheimer’s disease at age 50.

“He got so irritated with himself. His brain just wouldn’t work,” says Joe. “I would try and calm him and listen.” Over time, Joe watched Marty lose not only his memory, but eventually his life.

Joe is far from alone in experiencing this kind of loss. Alzheimer’s disease — a form of dementia — is the sixth leading cause of death in the U.S. And over the next 30 years, the number of people with Alzheimer’s is expected to almost triple.

His response to the loss, though, is singular. Joe started an annual square dancing event to raise money for Alzheimer’s research, part of a bargain he made with his brother.

“This is my calling. I’m following through on a promise to Marty, but I’m doing this for everyone,” says Joe.

Remember to Dance

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

Since the publication of this story, even more groundbreaking Alzheimer’s disease research at UW Medicine has happened. Sleep, it turns out, is critically important for the health of the brain. It’s becoming clear that an impaired glymphatic system — responsible for clearing away unwanted debris in the brain during sleep — can raise the risk of dementia. Several UW Medicine studies are underway that examine sleep-related interventions and treatments for Alzheimer’s disease. Additionally, a study from the UW Department of Pathology found a strong correlation between the presence of a protein called TDP-43 and the diagnosis of dementia in 80 and 90-year-olds. The study also provided new insight into brain resilience. To learn more, visit uwadrc.org.

Alzheimer’s and You

Know the Symptoms

Everyone forgets names and the location of their keys; it’s a natural part of aging. Still, it’s good to know the signs of Alzheimer’s, below.

“Around 30 percent of people, if they live long enough, will eventually develop dementia,” says Barak Gaster, M.D., UW professor of medicine. If memory loss interferes with your daily life, or if a one-time lapse seems to progress over time, you should see your doctor.

The Signs
• Memory loss; repeating questions.
• Poor judgement, leading to bad decisions.
• Loss of spontaneity and sense of initiative.
• Taking longer to complete normal daily tasks.
• Trouble handling money and paying bills.
• Wandering and getting lost; losing things or misplacing them in odd places.
• Mood and personality changes; increased anxiety and/or aggression.

From the National Institute on Aging

Be Ready — And Tell Your Family

“One of the most wrenching, difficult positions that a family faces,” says Gaster, “is when they have to guide the care of a loved one who isn’t able to understand the decisions before them.”

He and his colleagues have made this decision-making process much less fraught. After extensive collaboration with specialists at the Cambia Palliative Care Center of Excellence at the University of Washington, the UW Medicine Memory & Brain Wellness Center, and Kaiser Permanente Washington Health Research Institute, he created a dementia-specific living will, which guides people in thinking about their medical care should they be affected by dementia. The document explains different stages of the condition, and, for each stage, asks the reader what kind of care they’d like to receive. Readers are guided through considerations around resuscitation, going to the hospital and comfort care while receiving a frank assessment of the quality of life experienced by people with mild, moderate and severe dementia.

Gaster recommends that everyone over age 65 use this document, ideally before they show signs of dementia. And he advises all of us to share the document with our doctors and loved ones.

Related Article The New York Times: One Day Your Mind May Fade.

Advancing Brain Research

At UW Medicine, we’re working to understand the brain — and to find better, faster treatments for Alzheimer’s, traumatic brain injury, cancer and other conditions.