Large-Scale Analysis Links Glucose Metabolism Proteins to Alzheimer's Disease Biology

The largest study to date of proteins related to Alzheimer's disease published in Nature Medicine identified disease-specific proteins and biological processes that could be used to design new treatment targets and fluid biomarkers, reports ScienceDaily . The implication is that sets of proteins that regulate glucose metabolism, in conjunction with proteins related to the protective role of astrocytes and microglia, have a strong association with Alzheimer's pathology and cognitive impairment. The investigators analyzed protein expression patterns in more than 2,000 human brain samples and nearly 400 cerebrospinal fluid samples from healthy individuals and those with Alzheimer's. They marked groups, or modules, of proteins that reflect biological processes in the brain, then examined their relation to various pathologic and clinical features of Alzheimer's and other neurodegenerative diseases. Changes related to glucose metabolism and an anti-inflammatory response in glial cells were seen in brain samples from both people with Alzheimer's and those with documented brain pathology who were cognitively normal. This suggests that the anti-inflammatory processes designed to shield nerve cells may have been triggered in response to the disease. Moreover, higher concentrations of proteins involved in the way cells extract energy from glucose were in the spinal fluid of people with Alzheimer's. "This study exemplifies how research can be accelerated when multiple research groups share their biological samples and data resources," said U.S. National Institute on Aging Director Richard J. Hodes.