Dopamine, the brain’s so-called “feel-good” chemical, appears to play a significant role in Alzheimer’s disease, an Oklahoma Medical Research Foundation scientist found in a groundbreaking new study.
The discovery by Mike Beckstead, Ph.D., could someday provide a new pathway for ways to treat and even prevent the devastating neurological disease.
“We established definitively that long before the onset of symptoms, the dopamine neurons in the brain were far too active,” said Beckstead, who holds the Hille Family Foundation Chair in Neurodegenerative Disease Research at OMRF. “We also discovered both the cause for this overactivity and a potential solution.”
Beckstead’s new findings were published late last week in the online scientific journal Nature Communications.
According to the Alzheimer’s Association, nearly 7 million Americans live with the deadly, memory-robbing disease. That figure is projected to grow to more than 12 million by 2050.
Dopamine has many responsibilities in the brain, including body movement and signaling rewards. Disruption of dopamine can produce wide-ranging consequences, from depression and addiction to a separate neurological disease, Parkinson’s.
The connection between Alzheimer’s disease and dopamine was recently identified with new scientific techniques. Beckstead’s work is the first to identify a potential target to restore the dopamine system’s function.
Working with mice genetically engineered to develop a condition that mimics Alzheimer’s, Beckstead found that changes to dopamine neurons led to psychiatric changes.
“These findings support what clinicians have observed for a long time,” said Harris Blankenship, a Ph.D. student who contributed to the research. “People who eventually develop Alzheimer’s frequently experience mood and behavioral changes first, well before they exhibit problems with learning and memory.”
In Beckstead’s lab, the rodents’ brains developed two distinct signs of Alzheimer’s: plaques of a protein called amyloid beta, and tangles formed from a separate protein called tau. These hallmarks were present in the mice by 12 months of age, which equates to a middle-aged human.
“We also found that a different protein, CK2, caused the overactivity of the dopamine neurons,” Blankenship said. “By inhibiting CK2, we were able to restore those neurons to their normal function.”
Beckstead hopes these results will justify a longer project aimed at better illuminating how dopamine ties to the development of Alzheimer’s. “By understanding how communication involving dopamine neurons goes awry when Alzheimer’s strikes, we can target these processes to develop more effective therapies,” he said.
Courtney Griffin, Ph.D., OMRF’s vice president of research, believes the research could light the path for treating a significant unmet medical need.
“Unfortunately, the damage caused by Alzheimer’s often is well advanced before the person receives a diagnosis, which may explain why most medications developed so far haven’t proven very successful,” Griffin said. “If we really want to make a difference, we have to figure out what’s going on much earlier in the disease process. Dr. Beckstead’s research shows promise to lead us there.”
OMRF scientist Bill Freeman, Ph.D., contributed to this study, as did researchers at the University of Oklahoma Health Sciences Center.
These studies were funded by National Institutes of Health grant Nos. R21 AG072811, R01 AG052606, F31 AG079620, P30AG050911 and R01AG059430, U.S. Department of Veterans Affairs grant Nos. I01BX005396 and IK6BX006033, and funding from the Presbyterian Health Foundation and the Oklahoma Center for Adult Stem Cell Research.
