Strive to make discoveries that translate into tangible health benefits and improved quality of life
Dopamine is often called the “feel-good” chemical. That’s because the brain releases the neurotransmitter during activities we enjoy: eating a bowl of ice cream, achieving a goal, engaging in sexual activity.
Dr. Mike Beckstead had studied the physiology of dopamine his entire career, mostly in the context of drug addiction, where the chemical plays a pivotal role. But, he says, until 2017, “I would have told you that dopamine and Alzheimer’s weren’t connected.”
That year, a study came out in a scientific journal providing the first evidence the two might be linked. Beckstead was intrigued. And so was the National Institutes of Health. When he applied for a supplement on an existing research grant, the government awarded him funding to dig deeper into the question.
Not long after, Harris Blankenship was thinking about his graduate school plans. Then a senior at the University of Arkansas, he knew he wanted to study Alzheimer’s. “It’s one of the big, hard questions in neuroscience,” Blankenship says. But he thought that researchers and drug developers, who were largely centering their efforts on plaques and tangles that accumulate in the brains of those with the disease, might be focusing on the wrong thing.
Blankenship read about Beckstead’s new project and reached out to the OMRF scientist. “Mike was taking this new approach to a devastating disease we don’t understand. That sounded beautiful to me.” A conversation on Zoom confirmed Blankenship’s interest. “I thought, ‘I’ve got to work for this guy.’”
The feeling, says Beckstead, was mutual. “I was just getting the project. He was dying to do something. It made perfect sense.”
Blankenship enrolled at the University of Oklahoma Health Sciences Center, with Beckstead as his mentor. Beckstead promptly set his protégé to work to learn a vital laboratory technique, recording electrical signals from a single neuron. Beckstead assigned Blankenship to learn using mice genetically engineered to develop a condition that mimics Alzheimer’s. Almost immediately, the data Blankenship generated showed that something was different in the Alzheimer’s mice.
Over the next several years, Beckstead and Blankenship refined the studies, ultimately determining that the dopamine neurons in the Alzheimer’s mice fired faster than those in normal mice. They identified a protein that spurred the overactivity, then used a chemical inhibitor to restore dopamine activity to normal levels.
The resulting study, published in 2024 in the influential scientific journal Nature Communications, represents a major shift in how scientists think about Alzheimer’s. “We established definitively that long before the onset of symptoms, the dopamine neurons in the brain were far too active,” says Beckstead, who holds the Hille Chair in Neurodegenerative Disease Research. “We also discovered the cause for this overactivity and a potential solution.”
Moving forward, Beckstead is planning studies aimed at better illuminating how dopamine ties to the development of Alzheimer’s. “We’ve at least cracked the surface of something that might have a small effect on slowing down this terrible disease. With more work, maybe we can make a big difference instead of a little one.”
For Blankenship, who will earn his Ph.D. this spring and move to Boston for a postdoctoral fellowship, the experience has only whetted his appetite for discovery-based science. “For a brief moment, you are the only person in the world who knows something.” That singular feeling, though, is fleeting. “You rest on your laurels for four hours or so,” he says with a chuckle. That thought is quickly overtaken by another: “I need to do this experiment 100 more times so I’m sure it’s right.”
This might seem dispiriting to some. But to Blankenship, it’s just the opposite. “I feel like we just put one stone down in front of us in a stream. And now we can step on it.” With enough stones, they hope one day to reach the other side.
