It’s well-known that individuals with Type 2 diabetes are at an increased risk of developing Alzheimer’s disease, but the rationale why is not fully understood and is an area of current research.

Now, scientists at Wake Forest University School of Medicine have uncovered a novel mechanism that shows increased sugar intake and elevations in blood glucose are sufficient to cause amyloid plaque buildup within the brain, which increases the danger of Alzheimer’s disease. Amyloid plaque is made up of toxic proteins within the brain.

The study findings appear online in JCI Insight.

We wanted a greater understanding of the metabolic changes in diabetes that puts the brain in danger for Alzheimer’s disease or accelerates the pathology already forming within the brain of people who will go on to an Alzheimer’s disease diagnosis.”

Shannon Macauley, Ph.D., associate professor of physiology and pharmacology at Wake Forest University School of Medicine and principal investigator of the study

Using a mouse model, the research team demonstrated that more amyloid plaques form when sugar water is given as a substitute of standard drinking water. Additionally they found that elevations in blood sugar increase the production of amyloid-beta within the brain.

“This finding is important since it demonstrates that consuming an excessive amount of sugar is sufficient to cause amyloid plaque proliferation and increase the danger of Alzheimer’s disease,” Macauley said.

To raised understand the molecular drivers of this phenomenon, the research team identified a metabolic sensor on neurons that link changes in metabolism with neuronal firing and amyloid-beta production. The sensors are often called adenosine triphosphate (ATP)-sensitive potassium channels or KATP channels. ATP is an energy source that every one living cells must survive. These channels sense how much energy is offered for healthy function. Disrupting these sensors changes how the brain works normally.

“Using genetic techniques in mice, we removed these sensors from the brain and showed that elevation in blood sugar now not increased amyloid-beta levels or amyloid plaque formation,” Macauley said.

Next, researchers explored the expression of those metabolic sensors within the human Alzheimer’s disease brain and again found that the expression of those channels changes with an Alzheimer’s disease diagnosis.

In response to Macauley, the study suggests that these metabolic sensors may play a task in the event of Alzheimer’s disease and will ultimately result in latest treatments.

“What’s most notable is that pharmacological manipulation of those KATP channels may hold a therapeutic profit in reducing amyloid-beta pathology for diabetic and prediabetic patients,” said Macauley.

Source:

Atrium Health Wake Forest Baptist

Journal reference:

Grizzanti, J., et al. (2023) KATP channels are mandatory for glucose-dependent increases in amyloid-β and Alzheimer’s disease-related pathology. JCI Insight. doi.org/10.1172/jci.insight.162454.