Disease-specific proteins and biological processes have been identified by researchers at the National Institutes of Health (NIH) that could be developed into both new treatment targets and fluid biomarkers. These findings suggest that sets of proteins that regulate glucose metabolism, together with proteins related to a protective role of astrocytes and microglia, are highly associated with Alzheimer pathology and cognitive impairment.

The study involved measuring the levels and analyzing the expression patterns of more than 3000 proteins in a large number of brain and cerebrospinal fluid samples collected at multiple research centers across the United States.

The researchers analyzed patterns of protein expression in more than 2000 human brain and nearly 400 cerebrospinal fluid samples from both healthy people and those with Alzheimer disease. Following this, the researchers analyzed how protein modules relate to various pathologic and clinical features of Alzheimer and other neurodegenerative disorders.

Changes were seen in proteins related to glucose metabolism and an anti-inflammatory response in glial cells in brain samples from both individuals with Alzheimer disease as well as samples from individuals with documented brain pathology who were cognitively normal. These findings suggest that the anti-inflammatory processes designed to protect nerve cells may have been activated in response to the disease, according to the study authors.

In addition, the researchers found that the proteins involved in the way that cells extract energy from glucose are increased in the spinal fluid from people with Alzheimer disease. Many of these proteins were also elevated in people with preclinical Alzheimer, or those with brain pathology and no symptoms of cognitive decline.

The glucose metabolism and glial protein module were populated with proteins known to be genetic risk factors for Alzheimer disease, suggesting that the biological processes reflected by these protein families are involved in the actual disease process, according to the study authors.

“This large, comparative proteomic study points to massive changes across many biological processes in Alzheimer’s and offers new insights into the role of brain energy metabolism and neuroinflammation in the disease process,” said Suzana Petanceska, PhD, program director at NIA overseeing the AMP-AD Target Discovery Program, in a press release. “The data and analyses from this study has already been made available to the research community and can be used as a rich source of new targets for the treatment and prevention of Alzheimer’s or serve as the foundation for developing fluid biomarkers.”

REFERENCE
Large-scale analysis links glucose metabolism proteins in the brain to Alzheimer’s disease biology. NIH. https://www.nih.gov/news-events/news-releases/large-scale-analysis-links-glucose-metabolism-proteins-brain-alzheimers-disease-biology. Published April 13, 2020. Accessed April 15, 2020.