Researchers from Washington University School of Medicine in St. Louis, have determined that elevated blood sugar in the brain can harm brain function. The research study published in the Journal of Clinical Investigation is one of the first studies to reveal that elevated glucose in the blood can rapidly increase levels of amyloid beta, a key component of brain plaques in Alzheimer’s patients.
“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, a postdoctoral research scholar. “The link we’ve discovered could lead us to future treatment targets that reduce these effects.”
The researchers used mice models to investigate how elevated blood sugar might affect Alzheimer’s disease risk. In young mice without amyloid plaques in their brains, doubling glucose levels in the blood increased amyloid beta levels in the brain by 20 percent. The same condition in older mice caused amyloid beta levels to rise by 40%.
Spikes in blood glucose levels increase the activity of neurons in the brain, which promoted 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. Excessive firing in particular parts of the brain can increase amyloid beta production, lead to more amyloid plaques and foster the development of Alzheimer’s disease.
“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.”
Hyperglycemia modulates extracellular amyloid beta concentrations and neuronal activity in vivo, Macauley SL, Stanley M, Caesar EE, Yamada SA, Raichle ME, Perez R, Mahan TE, Sutphen CL, Holtzman DM., The Journal of Clinical Investigation, doi:10.1172/JCI79742, published online 4 May 2015.