Summary: Researchers have discovered a mechanism linking high sugar consumption to the risk of Alzheimer’s disease. The study found that elevated blood glucose and sugar levels can lead to the buildup of amyloid plaques in the brain — a hallmark of Alzheimer’s.
The study also revealed the role of neuronal ATP-sensitive potassium channels, or KATP channels, in this process. The manipulation of these channels may provide a new therapeutic approach to Alzheimer’s disease.
- High blood sugar and high blood sugar levels increase the risk of Alzheimer’s by encouraging the accumulation of amyloid plaques in the brain.
- The research team identified ATP-sensitive potassium channels (KATP channels) on neurons that link metabolic changes to amyloid-beta production in the brain.
- Pharmacological control of these KATP channels in diabetic and pre-diabetic patients may have potential therapeutic benefits.
Source: Wake Forest University
It is known that people with type 2 diabetes have a higher risk of developing Alzheimer’s disease, but the reason is not fully understood and is an ongoing area of research.
Now, Wake Forest University School of Medicine scientists have discovered a new mechanism that shows that increased sugar and blood glucose levels are enough to cause amyloid plaques to build up in the brain, which increases the risk of Alzheimer’s disease. Amyloid plaques are made up of toxic proteins in the brain.
The findings of the study are available online JCI Insight.
Shannon McAuley, Ph.D. “We need a better understanding of the metabolic changes in diabetes that accelerate the pathological process in the brains of individuals who are at risk of developing Alzheimer’s disease or who are already on their way to a diagnosis of Alzheimer’s disease.” 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 showed that more amyloid plaques formed when given sugar water than regular drinking water. They also found that high blood sugar levels increase amyloid-beta production in the brain.
“This finding is very important because it shows that excessive sugar intake is enough to increase the risk of amyloid plaques and Alzheimer’s disease,” said Macaulay.
To further understand the molecular drivers of this phenomenon, the research team identified a metabolic sensor that links metabolic changes in neurons to neuronal firing and amyloid-beta production.
The sensors are known as adenosine triphosphate (ATP)-sensitive potassium channels or KATP Channels. ATP is the source of energy that all living cells need to survive.
These channels determine how much energy is available for healthy function. Disabling these sensors changes how the brain works.
“Using genetic techniques in mice, we removed these sensors from the brain and showed that the increase in blood sugar levels stopped the increase in amyloid-beta levels or amyloid plaque formation,” said Macaulay.
Next, researchers examined the expression of these metabolic sensors in human Alzheimer’s disease brains and again found that the expression of these channels changes with the diagnosis of Alzheimer’s disease.
According to Macauley, the research suggests that these metabolic sensors may play a role in the development of Alzheimer’s disease and could eventually lead to new treatments.
“The most surprising thing about these KATP channels may hold therapeutic value in reducing amyloid-beta pathology in diabetic and pre-diabetic patients,” said Macaulay.
So Alzheimer’s disease research news
Author: Mira Wright
Source: Wake Forest University
Contact: Mira Wright – Wake Forest University
Image: Image credited to Neuroscience News.
Preliminary study: Open Access.
“KATP channels are important for glucose-dependent increases in amyloid-β and Alzheimer’s disease-related pathology.” Shannon Macaulay, et al JCI Insight
KATP channels are important for glucose-dependent increases in amyloid-β and Alzheimer’s disease-related pathology.
Elevated blood glucose levels, or hyperglycemia, may increase brain activation and amyloid-β (Aβ) release, providing a mechanistic link between type 2 diabetes and Alzheimer’s disease (AD).
Because the cellular mechanisms that regulate this relationship are not well understood, we investigated whether it is ATP-sensitive potassium (K).ATP) channels, which couple changes in energy supply to cellular excitability, play a role in AD pathogenesis.
First, we show K.ATP Channel subunits Kir6.2/KCNJ11 and SUR1/ABCC8 They are expressed in excitatory and inhibitory neurons and cortical expression in the human brain. KCNJ11 And ABCC8 Altered AD pathology in humans and mice.
Next, we examined neuronal K deletion.ATP Channel activity disrupts the relationship between metabolism, sensitivity, and Aβ pathology in a novel mouse model of cerebral amyloidosis and neuronal K.ATP Channel removal (ie, amyloid precursor protein [APP]/PS1 kir6.2–/– mouse).
Using both acute and chronic paradigms, we show that Kir6.2-K.ATP channels are metabolic sensors that regulate hyperglycemia-dependent interstitial fluid levels of Aβ, amyloidogenic processing of APP, and amyloid plaque formation.
These studies identify a new role for Kir6.2-K.ATP channels in AD and suggest pharmacological manipulation of Kir6.2-kATP channels hold therapeutic promise in reducing Aβ pathology in patients with diabetes or prediabetes.