Although Alzheimer’s disease is the leading cause of dementia among older people around the globe, much about the condition is still a mystery – including a cure. This week, new research uncovered more about the connection between glucose and Alzheimer’s, paving the way for possible new treatments.
“In this study, we revealed an underappreciated role of glucose within pigment glia to regulate their inflammatory responses,” explained researchers from Tokyo Metropolitan University in the study published Tuesday in the Disease Models & Mechanisms journal. Their team was led by Professor Kanae Ando.
Pigment glia are cells inside the retina. Specifically, glial cells are described by the National Cancer Institute as “any cells that hold nerve cells in place and help them work the way they should,” and types of these cells include oligodendrocytes, astrocytes, microglia, and ependymal cells.
In the U.S., nearly 7 million Americans are already living with Alzheimer’s disease, and that number is expected to double by 2060. There is no cure for the condition, but there are two medications available that can help slow the cognitive and functional decline that characterizes the disease. Some research indicates that artificial light might be a risk factor for developing the condition, among many other factors.
“Scientists are working against the clock to unravel the vast network of mechanisms by which AD affects our nervous system,” said a press release about the new research. “We know, for example, that AD is characterized by a build-up of tau protein inside cells, but the ways in which this leads to neurodegeneration are not yet fully understood.”
One of those mysteries revolves around glial cells, which are known to clear up abnormal buildups of protein. These cells also help neurons stay fueled by metabolizing glucose, meaning that they use sugar for energy. A major drop in brain glucose metabolism is observed in Alzheimer’s patients, but scientists didn’t understand how that drop was related to something called tau protein buildup that is a feature of Alzheimer’s.
In an article from last September, the National Institutes of Health covered possible connections between glucose metabolism and Alzheimer’s disease. It said that misfolded amyloid protein (another feature of Alzheimer’s) and tau proteins increased levels of the IDO1 protein coding gene an activity in astrocytes. Furthermore, researchers found that the proteins suppressed the conversion of glucose to lactate. By inhibiting IDO1 or turning off the gene that encodes it, lactate production was restored.
A press release about the new study explained that the research team used fruit fly retinas to examine the impact of tau, a protein that helps stabilize the internal skeleton (a tube-like shape through which nutrients and other essential substances travel to reach different parts of the neuron) of nerve cells. While it has an important role, an abnormal buildup of tau that can cause the collapse of that internal skeleton associated with Alzheimer’s, according to the Alzheimer’s Association.
Within the fruit fly retinas, researchers found that buildup of tau protein was linked with neurodegeneration, swelling in nearby regions, and the formation of abnormal inclusions.
“They were able to show that the latter of these was caused by glial cells being abnormally active,” said the press release. “To explore how this related to its glucose metabolism, they were able to use genetic modification techniques to express more of a glucose transporting protein (GLUT) in glial cells.”
The team was amazed at the results. There wasn’t a change to tau buildup, but the genetic modification came with a suppression of neurodegeneration and less inflammation.
“This shows that tau-protein build-up causes glial cells to suffer from a significant drop in glucose metabolism,” the press release explained. Therefore, the team suggests that “glial glucose metabolism might be a new target for novel therapies for neurodegenerative conditions,” including Alzheimer’s and Parkinson’s disease.