Mental Health

Having Diabetes Can Increase Your Alzheimer's Risk Via Blood Glucose And Brain Plaque Link

Alzheimer's Disease
Developing diabetes can also increase our risk for Alzheimer's disease. Photo courtesy of Shutterstock

Interrelated chronic diseases are nothing new to health care professionals. It’s no secret developing obesity can also increase our risk for diabetes and heart disease. However, the relationship between a neurological condition, such as Alzheimer’s disease, and a metabolic condition, such as diabetes, is a bit more complicated. Researchers from Washington University School of Medicine in St. Louis have found a new link between diabetes and Alzheimer’s.

"Our results suggest that diabetes, or other conditions that make it hard to control blood sugar levels, can have harmful effects on brain function and exacerbate neurological conditions such as Alzheimer's disease," Dr. Shannon Macauley, a postdoctoral research scholar, said in a statement. "The link we've discovered could lead us to future treatment targets that reduce these effects."

Macauley and her colleagues introduced high levels of glucose into the bloodstreams of mice that were bred to develop a condition resembling Alzheimer’s. The research team set out to determine how elevated blood sugar can also lead to a rise in amyloid beta levels. Amyloid beta is often tied to the buildup of brain plaque, which is considered an earlier driver of the changes in the brain caused by Alzheimer’s.

Mice with no trace of amyloid plaque in their brain prior to the experiment had the amyloid beta levels in their brains amplified by 20 percent after having the glucose levels in their blood doubled. In the same experiment with older mice that had already developed brain plaque, researchers found that their levels of amyloid beta had increased by 40 percent. Upon closer investigation they showed that amyloid beta production was promoted by higher blood glucose increasing the activity of neurons in the brain.

Firing of neurons in the brain is how brain cells encode and transmit information, however, unnecessary firing in certain areas of the brain can lead to increased production of amyloid beta which, subsequently, leads to more amyloid plagues and the development of Alzheimer’s. Unnecessary firing of neurons is often the result of openings on the surface of brain cells known as KATP channels which are responsible for changes in amyloid beta when blood sugar increases.

"Given that KATP channels are the way by which the pancreas secretes insulin in response to high blood sugar levels, it is interesting that we see a link between the activity of these channels in the brain and amyloid beta production," Macauley added. "This observation opens up a new avenue of exploration for how Alzheimer's disease develops in the brain as well as offers a new therapeutic target for the treatment of this devastating neurologic disorder."

In the second part of the experiment, the researchers gave the mice diazoxide, a glucose-elevating drugs that is often used to treat low blood sugar, by injecting directly into the brain. While elevated glucose causes KATP channels to close which, in turn, excites brain cells, the diabetes drug resulted in these channels staying open. Further research conducted by Macauley’s team will focus on treating Alzheimer’s-stricken mice with drugs used to treat diabetes.

Source: Stanley M, Caesar E, Macauley S, et al. Hyperglycemia modulates extracellular amyloid-β concentrations and neuronal activity in vivo. The Journal of Clinical Investigation. 2015. 

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