Study links glucose metabolism proteins in the brain to Alzheimer’s disease biology

A team of scientists from the Emory School of Medicine appeared to put another piece of the puzzle in place to predict and treat Alzheimer’s disease with a new finding that identified disease-specific proteins and biological processes that could be developed into both new treatments and biomarkers.

A biomarker is an indicator of a progressing disease, infection or exposure.

"The findings suggest that sets of proteins that regulate glucose metabolism (stored energy that powers the brain along with red blood cells), together with proteins related to a protective role of astrocytes and microglia — the brain’s support cells — are strongly associated with Alzheimer’s pathology and cognitive impairment,” a communique announcing the new findings from the National Institute of Health stated.

An Emory School research team led by doctors Erik C.B. Johnson, Nicholas T. Seyfried and Allan Levey analyzed the patterns of behavior in proteins in brain samples from 2,000 subjects and nearly 400 cerebrospinal fluid samples collected from both healthy people and those with Alzheimer’s disease. The study identified groups of proteins that reflect biological processes in the brain.

The paper’s authors included medical researcher Madhav Thambisetty, chief of Clinical and Translational Neuroscience Section at the National Institute on Aging (NIA)’s Laboratory of Behavioral Neuroscience in Maryland.

Researchers were able to spot changes in the proteins related to glucose metabolism and an anti-inflammatory response in cell brain samples taken from both people with Alzheimer’s as well as in samples from individuals with documented brain pathology (disease) but who otherwise were cognitively normal.

The research study noted, “This suggests anti-inflammatory processes designed to protect nerve cells may have been activated in response to the disease. The proteins involved in the way cells extract energy from glucose are increased in the spinal fluid from people with Alzheimer’s.”

The findings stated that many of these proteins were also elevated in people with preclinical Alzheimer’s, individuals with brain pathology but without symptoms of cognitive decline.

“Importantly, the glucose metabolism was populated with proteins known to be genetic risk factors for Alzheimer’s, suggesting that the biological processes reflected by these protein families are involved in the actual disease process,” the findings explained.

The result appears to have moved researchers a step closer to identifying Alzheimer’s in its earlier stages of development.

“We’ve been studying the possible links between abnormalities in the way the brain metabolizes glucose and Alzheimer’s-related changes for a while now,” Thambisetty said. “The latest analysis suggests that these proteins may also have potential as fluid biomarkers to detect the presence of early disease.”

Alzheimer's disease is a type of dementia that causes problems with memory, thinking and behavior. Symptoms usually develop slowly and get worse over time, caused by the death of brain cells.

Considered a “neurodegenerative disease,” the condition results in fewer and fewer nerve cells and connections over time.