You are here

Scientists Find Link Between Diabetes and Alzheimer’s Disease

Elevated blood sugar may contribute to AD development

Investigators have uncovered a connection between diabetes and Alzheimer’s disease (AD), providing further evidence that an illness that robs people of their memories may be affected by elevated blood sugar, according to scientists at Washington University School of Medicine in St. Louis.

While earlier studies have pointed to diabetes as a possible contributor to AD, the new study (conducted in mice) shows that elevated glucose in the blood can rapidly increase levels of amyloid beta, a key component of brain plaques in AD patients. The buildup of plaques is thought to be an early driver of the complex set of changes that AD causes in the brain.

The new research was published May 4 in the Journal of Clinical Investigation.

“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,” said lead author Shannon Macauley, PhD. “The link we've discovered could lead us to future treatment targets that reduce these effects.”

People with diabetes can’t control the levels of glucose in their blood, which can spike after meals. To understand how elevated blood sugar might affect the risk of AD, the researchers infused glucose into the bloodstreams of mice bred to develop an AD-like condition.

In young mice without amyloid plaques in their brains, doubling glucose levels in the blood increased levels of amyloid beta in the brain by 20%.

When the scientists repeated the experiment in older mice that already had developed brain plaques, amyloid beta levels increased by 40%.

The researchers also found that spikes in blood glucose increased the activity of neurons in the brain, which promoted the production of amyloid beta. One way the firing of such neurons is influenced is through openings called KATP channels on the surface of brain cells. In the brain, elevated glucose causes these channels to close, which excites the brain cells, making them more likely to fire.

Normal firing is how a brain cell encodes and transmits information. But excessive firing in particular parts of the brain can increase the production of amyloid beta, which can lead to more amyloid plaques, thereby promoting the development of AD.

To show that KATP channels are responsible for the changes in amyloid beta in the brain when blood sugar is elevated, the scientists gave the mice diazoxide, a glucose-elevating drug commonly used to treat low blood sugar. To bypass the blood–brain barrier, the drug was injected directly into the brain.

Diazoxide forced the KATP channels to stay open even as glucose levels rose. The production of amyloid beta remained constant, contrary to what the researchers typically observed during a spike in blood sugar, providing evidence that the KATP channels directly link glucose, neuronal activity, and amyloid beta levels.

“Given that KATP channels are the way by which the pancreas secretes insulin in response to high blood sugar levels, it is interesting that we see a link between the activity of these channels in the brain and amyloid beta production,” Macauley said. “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.”

The researchers are also investigating how changes caused by increased glucose levels affect the ability of brain regions to network with each other and complete cognitive tasks.

Source: Medical Xpress; May 4, 2015.

Recent Headlines

Despite older, sicker patients, mortality rate fell by a third in 10 years
Study finds fewer than half of trials followed the law
WHO to meet tomorrow to decide on international public heath emergency declaration
Study of posted prices finds wild variations and missing data
Potential contamination could lead to supply chain disruptions
Declining lung cancer mortality helped fuel the progress
Kinase inhibitor targets tumors with a PDGFRA exon 18 mutation
Delayed surgery reduces benefits; premature surgery raises risks
Mortality nearly doubled when patients stopped using their drugs