Connection Between Alzheimer’s Disease and Diabetes Uncovered in Recent Research

Ana de Barros, PhD avatar

by Ana de Barros, PhD |

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Azeliragon, Alzheimer's, diabetes

In a recent study published in The Journal of Clinical Investigation, a team of researchers at the Washington University School of Medicine in St. Louis found an association between Alzheimer’s disease and diabetes, which provides evidence on the fact the Alzheimer’s may be affected by elevated blood sugar.

This new study conducted in mice revealed that increased levels in glucose in the blood increased the levels of amyloid beta, a key feature of brain plaques in patients with Alzheimer’s disease.

“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,” said lead author Shannon Macauley, PhD, a postdoctoral research scholar in a recent news release “The link we’ve discovered could lead us to future treatment targets that reduce these effects.”

Diabetes causes uncontrolled glucose levels in the blood, so many patients rely on insulin and other drugs to maintain their blood sugar levels controlled.

In their investigation, the researchers infused glucose in mice models of Alzheimer’s disease, with results showing that in young mice without amyloid plaques in their brains, doubling glucose levels in the blood resulted in an increase of 20% of amyloid beta levels in the brain. Then, in older mice that already had developed brain plaques, they repeated the experiment and found amyloid beta levels increased by 40%.

The results also revealed that spikes in the levels of glucose increased the activity of neurons, which caused amyloid beta production. Elevated glucose causes the closing of KATP channels, located on the brain cells surface, also causing excitement of brain cells. Normal “firing” of brain cells results in the transmission of information. However, when there is a dysfunction in this mechanism, there is an increase in the production of amyloid beta, leading to the development of Alzheimer’s disease.

The scientists gave diazoxide to the mice, to assess if KATP channels are responsible for the changes in amyloid beta in the brain when blood sugar is elevated. The drug, commonly used to treat low blood sugar was injected directly

The compound make the KATP channels to remain open even when there was high levels of glucose, with results showing that the KATP channels directly link glucose, neuronal activity and amyloid beta levels.

“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 said. “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.”

The team is now looking to understand how alterations in glucose levels affect the capacity of brain regions to network with each other and complete cognitive tasks.