By Paul Ian Cross, Ph.D. — Fact checked by Alexandra Sanfins, Ph.D.
Type 2 diabetes is known to increase the likelihood of developing Alzheimer’s disease, but the underlying reasons remain unclear and are subject to ongoing research.
Now, scientists at Wake Forest University School of Medicine in North Carolina have made a significant breakthrough, demonstrating that increased sugar consumption and elevated blood glucose levels alone can trigger the accumulation of amyloid plaque in the brain, which is a contributing factor to the risk of Alzheimer’s disease.
The researchers focused on a type of channel called ATP-sensitive potassium (KATP) channels, which are involved in regulating cell activity based on energy levels. In the brain, KATP channels are strongly expressed in the neuronal circuitry.
In a mouse model, the researchers demonstrated that the consumption of sugar water, as opposed to regular drinking water, leads to a greater formation of amyloid plaques.
Additionally, they discovered that elevated blood sugar levels contribute to increased production of beta-amyloid in the brain.
Investigating the underlying mechanisms, the research team identified a group of metabolic sensors called ATP-sensitive potassium channels, or KATP channels, present in neurons. These channels act as a connection between metabolic changes, neuronal activity, and the production of beta-amyloid in the brain.
Functioning as energy regulators, these KATP channels monitor the availability of ATP, a vital energy source for cellular survival.
Disturbing the normal function of these sensors can disrupt the brain’s regular operations and have implications on its overall functionality.
Subsequently, the researchers investigated the expression of these metabolic sensors in the brains of individuals diagnosed with Alzheimer’s disease, and once again observed alterations in the presence of these channels.
Dr. Shannon Macauley, associate professor of physiology and pharmacology at Wake Forest University School of Medicine and the study’s principal investigator, explained the background to Medical News Today, saying: “We know that individuals with type 2 diabetes are at a greater risk for developing Alzheimer’s disease. And for decades, scientists have explored why. What is it about the metabolic changes in diabetes that puts the brain at risk for Alzheimer’s disease?”
“Using mouse models, we demonstrate that elevations in blood sugar increase the production of beta-amyloid in the brain; this is a toxic protein that makes up amyloid plaques, a hallmark of Alzheimer’s disease. In a chronic experiment, if mice are given sugar water instead of regular drinking water, they form more amyloid plaques than mice who drink regular water. This was interesting because this was independent of any change in their diet otherwise. It demonstrates that consummating too much sugar is enough to cause amyloid plaque proliferation and increase the risk of Alzheimer’s disease.”
– Dr. Shannon Macauley
Dr. Macauley and the team then asked: “What were the molecular drivers of this phenomenon?”
“We identified a metabolic sensor on neurons, known as ATP-sensitive potassium channels or KATP channels, that link changes in metabolism with excitability and abeta production,” Dr. Macauley explained.
“Using genetic techniques in mice, we removed these sensors from the brain and showed that elevation in blood sugar did not results in increased beta-amyloid levels or amyloid plaques. We then explored in [the] expression of these metabolic sensors in human [Alzheimer’s] patient brains post-mortem and found that the expression of these channels changes with an Alzheimer’s diagnosis, again suggesting these metabolic sensors may play a role in the development of Alzheimer’s disease,” the researcher added.
Kristen Carli, a registered dietitian nutritionist, not involved in this research, told MNT that “this study highlights how influential KATP channels are to the impact of hyperglycemia on the risk of developing Alzheimer’s.”
Dr. David Merrill, a geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica, CA, also not involved in the study, said: “These new findings help explain why patients with diabetes are at higher risk of Alzheimer’s disease. The high blood sugar is driving the formation of beta-amyloid plaques.”
“Alzheimer’s disease is the end result of a prolonged period of sub-optimal health. In this case, the culprit is diabetes. In other cases, there are other culprits. Patients and their doctors need to be more curious about what is causing beta-amyloid plaques to form in the brain.”
Dr. David Merrill
Dr. Macauley notes that the research “not only […] offer[s] one explanation of why individuals with type 2 diabetes are at increased risk for Alzheimer’s disease, [but] it uncovers a possible therapeutic target for treating Alzheimer’s disease.”
Dr. Merrill highlighted how “early identification and correction of underlying drivers of Alzheimer’s disease, like [a] suboptimal elevation of blood sugar levels and the associated insulin resistance, may be more effective than treatments aimed at cleaning up the mess of plaques that are left behind once the synapses and neurons are already dead and gone.”
“Teaching patients how different foods impact their blood sugar levels may help them avoid developing diabetes now and Alzheimer’s later,” Dr. Merrill explained.
Carli pointed out that pharmaceutical companies could potentially develop medicines that target the KATP channels, particularly for patients with type 2 diabetes.
“Theoretically, by targeting the KATP channels, the drugs could reduce the impact that hyperglycemia has on the release of beta-amyloid, which is directly related to the risk of developing Alzheimer’s disease,” Carli explained.
“As a registered dietitian, I’m inclined to wonder how this will affect the desire for those with type 2 diabetes to change and alter their diet. Even if the risk of Alzheimer’s disease is completely eliminated for those with hyperglycemia, there are many other health concerns that result from elevated blood glucose. I would hope that by creating drugs to reduce risk of Alzheimer’s disease, these patients still focus on making healthy changes to their diets to reduce hyperglycemia.”
– Kristen Carli
This article originally appeared here and was republished with permission.