Forgetting the name of a loved one may be one of the first signs people notice of dementia, but it’s rarely the first warning sign your brain gives. Changes in the brain that lead to neurodegenerative diseases like Alzheimer’s and dementia start showing up decades before symptoms arrive, and the chemicals at work inside the body can often tip us off to these changes well ahead of time.
A recent study found that a blood protein called GDF15, which is released when cells are under stress, could serve as one of the earliest warning signs of dementia. After tracking more than half a million people for 15–25 years, researchers discovered that those with higher GDF15 levels before age 55 were significantly more likely to develop dementia later in life. Finding that protein in the blood was a much stronger predictor of vascular dementia than Alzheimer’s disease and related dementia.
This opens the possibility that a simple blood test in midlife, one that checks for GDF15, could help doctors flag who is at higher risk of dementia decades down the line. The findings are published in Science Advances.
Just an indicator or a driver too?
Protein biomarkers have gained significant attention in recent years as potential tools for diagnosing Alzheimer’s and other dementia disorders. A major study examined the proteome, the full set of proteins in the blood, and found that disruptions in proteins associated with metabolism, synaptic communication and the immune system were measurable as early as 20 years before diagnosis.
Among the thousands of proteins analyzed, GDF15 (macrophage inhibitory cytokine-1, or MIC-1) emerged as a standout signal tied to dementia risk. This stress-responsive protein circulates in the blood and is closely connected to aging, inflammation, metabolism and a spectrum of age-related conditions. What remained uncertain was whether GDF15 is simply a marker of risk or plays a direct role in dementia.
Tracking risk across populations
In this study, researchers investigated whether GDF15 is more strongly linked to one type of dementia than others. The scientists analyzed data from six independent groups across different countries, including the United States, Iceland, the United Kingdom and Japan. For the next 15–20 years, they tracked which participants eventually developed dementia, distinguishing between types like Alzheimer’s disease and vascular dementia. They also conducted brain scans and spinal fluid tests to map the brain’s physical and chemical changes.
Across multiple cohorts, higher plasma GDF15 levels consistently predicted a greater risk of all-cause dementia, whether measured in midlife or later life. The association was particularly strong for vascular dementia, while the link with Alzheimer’s disease was comparatively weaker. Beyond predicting dementia risk, elevated GDF15 was associated with brain shrinkage and small vessel damage as detected in neuroimaging, even among people who still had normal memory and thinking skills.
Clues to a biological role
To investigate exactly how GDF15 affects the brain, researchers conducted lab tests in which they exposed human immune cells to the protein to observe their responses. They discovered that GDF15 not only altered the cells’ metabolic pathway but also weakened their natural antiviral response.
The researchers note that these findings strengthen the case for GDF15 as a promising biomarker for cognitive decline while also revealing the biological pathways that may link it to dementia risk. Before adoption into a clinical framework, further studies are needed to validate GDF15 as an early-life risk signal in more diverse populations and across health care settings. https://medicalxpress.com/news/2026-06-blood-protein-flag-dementia-decades.html
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