Many chemical biomarkers circulate in the body and can indicate how health may develop over time. These markers help researchers and physicians detect risks for certain conditions before symptoms appear, allowing for earlier management or prevention. A large international study has identified one such marker that predicts dementia when measured in middle age. The protein, known as GDF15 and present in blood plasma, was examined across six major cohort studies. Individuals with higher levels at age 55 or younger showed greater likelihood of developing dementia years later. The researchers propose that GDF15 influences metabolic pathways and the neuroimmune system. Prior work had already connected elevated GDF15 to later dementia, yet the new analysis extends the link to ages below 55. Data came from studies in the United States, United Kingdom, Iceland, and Japan, with follow-up periods of 15 to 25 years. The association proved strongest for vascular dementia, possibly tied to inflammation. Genetic analysis using Mendelian randomization confirmed that variants linked to higher GDF15 also raised dementia risk, independent of lifestyle or environment. Additional checks of brain scans and cerebrospinal fluid revealed correlations between blood and fluid levels of the protein, along with greater brain shrinkage. Laboratory tests on immune cells suggested GDF15 disrupts normal immune and energy pathways. While the protein normally helps regulate immune responses, excessive suppression may leave the brain more vulnerable. The findings support GDF15 as an early biomarker, especially for vascular dementia and neuroinflammation. The study appears in Science Advances.
