Jefferson Kinney’s research into Alzheimer’s disease is among the projects getting a big boost through an $11.1 million grant to fund a Center of Biomedical Research Excellence, the first in Southern Nevada. UNLV and the Cleveland Clinic Lou Ruvo Center for Brain Health were recently awarded the grant from the National Institute of Health and National Institute of General Medical Sciences.
It's just one of several lines of research that Kinney's UNLV laboratory is working on related to Alzheimer's disease. Here, Kinney discusses the results of one of his latest studies — and why they are both surprising and promising.
Alzheimer’s disease is a debilitating disorder that affects millions of people. A number of risk factors have been identified for Alzheimer’s disease; however, the role they play in the onset and progression of the disease is unclear. Two of the greatest risk factors are diabetes mellitus (specifically Type 2 diabetes) and chronic inflammation.
Two decades, researchers effectively linked a higher likelihood of Alzheimer’s disease with Type 2 diabetes. More recently, they’ve found that chronic inflammation in the brain is linked to the onset and acceleration of Alzheimer’s disease. The mechanisms underlying how these two risk factors contribute to Alzheimer’s disease are unclear and there has been very little research in this area.
"In the clinic, a large number of (Alzheimer's disease) patients have diabetes and chronic inflammatory states going on at the same time,” said Jefferson Kinney, a UNLV neuroscience researcher and professor in the psychology department. "What we want to see is, if the two risk factors were simultaneously present, would that accelerate Alzheimer's disease characteristics?”
Kinney’s research team used animal models to seek out answers. The results, recently published in the journal Neuropharmacology, were quite positive, but not at all what the group anticipated. The findings revealed a new path for future studies to explore.
Kinney’s animal model included four groups of rodents. The first (control) group showed no behaviors or pathologies consistent with Alzheimer’s disease. The second group was treated to disrupt insulin signaling in the brain, similar to Type 2 diabetes. This group exhibited both behavioral and pathological changes consistent with Alzheimer’s disease, supporting the link between diabetes and Alzheimer’s disease.
The third group was administered a compound to induce a brief activation of the immune system, akin to making them a little sick for a brief time. The final group had both the insulin disruption and given the same immune-activating agent as the third group, to combine the risk factors. All animals were then evaluated for behavioral and pathological changes consistent with Alzheimer’s disease.
The team anticipated the combined (fourth) group would exhibit the most severe disruptions; however, exactly the opposite occurred. Kinney’s team found that learning deficits and the Alzheimer’s disease pathologies of the fourth group were less severe than the diabetes alone group.
“They did significantly better than the diabetic group,” he said. “The symptoms were mild compared to controls.” That brief sickness “rescued” some of the learning deficits and Alzheimer’s pathology that the diabetic state had induced.
The Take Away
The study found that a brief activation of the immune system (inflammation) is actually a way to fight off deficits associated with Alzheimer’s disease. However, as is the case with chronic brain inflammation in the human body, when that immune response extends for a longer period of time, it reverses gains and fuels further neurological decline.
But Kinney says the results have motivated his team to continue down this research trail. Follow-up studies will look more closely at what length of time immune activation starts to become a problem and what mechanisms are responsible for both the improvement and eventual worsening of Alzheimer’s pathology.
“This caught some fire for us. There are a lot of directions we can go from here,” he added.