The Role of Metabolic Sensors in Alzheimer’s

It is commonly recognized that patients with type 2 diabetes are more likely to develop Alzheimer’s disease, although the cause for this is not entirely understood and is currently being researched. Recently, scientists identified that metabolic sensors may play a role in the development of Alzheimer’s disease.

Wake Forest University School of Medicine researchers have discovered a novel method through which increased sugar intake and blood glucose levels are sufficient to trigger amyloid plaque accumulation in the brain, increasing the risk of Alzheimer’s disease. Amyloid plaque is a harmful protein buildup in the brain.

The study results are available online in JCI Insight.

“We wanted a better understanding of the metabolic changes in diabetes that put the brain at risk for Alzheimer’s disease or accelerates the pathology already forming in the brain of individuals who will go on to an Alzheimer’s disease diagnosis,” said 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 researchers revealed that when sugar water is provided instead of regular drinking water, more amyloid plaques form. They also discovered that high blood sugar levels stimulate the development of amyloid-beta in the brain.

This finding is significant because it demonstrates that consuming too much sugar is enough to cause amyloid plaque proliferation and increase the risk of Alzheimer’s disease,” Macauley said.

The researchers discovered a metabolic sensor on neurons that links changes in metabolism with neuronal firing and amyloid-beta formation in order to better understand the molecular drivers of this phenomena. Adenosine triphosphate (ATP)-sensitive potassium channels, or KATP channels, are the sensors. All living cells require ATP as an energy source in order to survive. These channels detect the amount of energy available for healthy function. Disrupting these sensors alters how the brain typically functions.

“Using genetic techniques in mice, we removed these sensors from the brain and showed that elevation in blood sugar no longer increased amyloid-beta levels or amyloid plaque formation,” Macauley said.

The researchers next investigated the expression of these metabolic sensors in the human Alzheimer’s disease brain and discovered that the expression of these channels changes with Alzheimer’s disease diagnosis.

The discovery, according to Macauley, implies that these metabolic sensors may play a role in the development of Alzheimer’s disease and may eventually lead to new treatments.

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

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