Discovery links glucose metabolism abnormalities to Alzheimer’s disease

A new study, funded by the National Institutes of Health’s National Institute on Aging, is offering novel insights into how protein expressions can be altered during the course of Alzheimer’s disease. The research suggests proteins regulating glucose metabolism and the anti-inflammatory activity of brain immune cells are linked with Alzheimer’s pathology, and could point researchers toward new treatment and diagnostics.

The study, published in the journal Nature Medicine, comes out of a larger project called the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD). This NIH-led venture is designed to advance novel diagnostic and treatment targets while bringing together government, industry, and nonprofit organizations.

This new paper describes the results of the largest Alzheimer’s-related protein study conducted to date, gathering over 2000 brain tissue samples and around 400 cerebrospinal fluid samples from research centers across the United States. Expression patterns of more than 3000 proteins were measured, looking at differences between healthy subjects and Alzheimer’s patients at different stages of the disease.

“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,” explains Suzana Petanceska, the NIA director managing the AMP-AD Target Discovery Program.

In both cerebrospinal fluid and brain tissue samples the research revealed higher expressions in Alzheimer’s patients of proteins involved in glucose metabolism and anti-inflammatory processes. Importantly, these elevated protein levels were also detected in subjects with preclinical Alzheimer’s, suggesting as well as a potential new treatment target, the protein abnormalities could serve as an effective early-stage biomarker of the disease.

“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,” say Madhav Thambisetty, one of the authors on the new study. “The latest analysis suggests that these proteins may also have potential as fluid biomarkers to detect the presence of early disease.”

The researchers note this study describes what is known as a fundamental research finding. This essentially means the study is outlining a foundational discovery, from which future research will hopefully be able to build new treatments or diagnostics. Suzana Petanceska notes this work has already been spread around the Alzheimer’s research community with the goal of inspiring new treatment targets.

“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,” she concludes.

The study was published in the journal Nature Medicine.

Source: NIH

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