Could high blood sugar be a cause of Alzheimer's disease?

While nobody knows exactly what causes the complex brain changes that lead to Alzheimer's disease, scientists suspect one of the drivers is the accumulation of plaques of a faulty protein called beta-amyloid. Now, a new study of mice shows how too much sugar in the blood can speed up the production of the protein.

The researchers suggest their findings will lead to new treatments that reduce the harmful effects of high blood sugar on the brain.

Earlier studies have pointed to diabetes - where the body fails to control high blood sugar naturally with insulin - as a possible contributor to Alzheimer's disease, but the new study links high blood sugar itself to beta-amyloid.

Researchers from the School of Medicine at Washington University in St. Louis (WUSTL) report their findings inThe Journal of Clinical Investigation.

Lead author and postdoctoral research scholar Dr. Shannon Macauley says:

"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."

She and her colleagues suggest their finding could lead to new treatment targets to reduce the harmful effects of high blood sugar on the brain.

Doubling of blood glucose led to 20% higher levels of beta-amyloid

For their study, the team used mice bred to develop a condition that is like Alzheimer's in humans - as they age their brains accumulate amyloid plaques.

When they infused glucose into the bloodstream of young mice, they found their brains produced beta-amyloid faster. A doubling of blood glucose led to 20% higher levels of beta-amyloid compared with mice that had normal blood glucose levels.

When the team repeated the experiment in older mice that already had amyloid plaques in their brains, beta-amyloid levels rose by 40%.

Closer examination revealed that sudden elevation of blood sugar increased brain cell activity, which stimulates them to make more beta-amyloid.

The team found that openings called KATP channels were an important feature of increased beta-amyloid. These ATP-sensitive potassium channels sit on the surface of brain cells and close when glucose levels get too high. When the channels are closed, the neurons are more likely to fire.

Under normal conditions, neurons fire to encode and send information - a basic function essential for learning and memory. But too much firing in certain areas of the brain increases beta-amyloid, which makes it more likely that plaques will form and encourage the development of Alzheimer's, the authors suggest.

KATP channel 'directly links glucose, brain cell activity and beta-amyloid'

In a final set of experiments, the team injected diazoxide straight into the brains of mice (to bypass the blood brain barrier). Diazoxide is a glucose-elevating drug that is used to treat low blood sugar.

The drug forced the KATP channels to stay open as glucose levels rose. Under these conditions, the brain cells produced beta-amyloid at the normal rate - it did not speed up.

The team concludes this result shows that the KATP channel directly links glucose levels with brain cell activity and rate of beta-amyloid production.

The researchers are already exploring the link further using diabetes drugs in Alzheimer's-like mice.

KATP channels feature in all kinds of cells, not just brain cells. For example, they feature in the pancreatic cells that make insulin - the enzyme the body uses to control blood sugar.

Commenting on the contribution of their findings, Dr. Macauley says:

"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."

She and her colleagues are also looking into how raised glucose levels may interfere with how different parts of the brain work together in cognitive functioning.

Funds for the study came from the National Institutes of Health, the National Science Foundation and the JPB Foundation.

Meanwhile, Medical News Today recently learned how scientists at Johns Hopkins University found a molecule that links high blood sugar to metabolic disease. Writing in the Proceedings of the National Academy of Sciences, the team says the discovery could lead to new ways to prevent and treat diabetes.