Study Identifies GDF15 as a Potential Early Blood Marker for Dementia

A study published in Science Advances suggests that a blood protein known as growth differentiation factor 15 (GDF15) could help identify people at increased risk of developing dementia many years before symptoms emerge. Drawing on data from several large international population studies, researchers found that higher levels of GDF15 in midlife were associated with a greater likelihood of being diagnosed with dementia later in life.

GDF15 is a protein found in blood plasma that is involved in regulating immune responses and maintaining cellular health. The findings indicate that elevated levels of this protein may serve as an early warning sign of future cognitive decline, particularly for vascular dementia.

Large Population Studies Identified an Early Warning Signal

The researchers combined data from six long-term cohort studies conducted in the United States, the United Kingdom, Iceland, and Japan. Together, the studies included tens of thousands of participants who provided blood samples and were monitored through health records for periods ranging from 15 to 25 years.

Among participants aged 55 years or younger, those with higher concentrations of GDF15 in their blood were more likely to develop dementia in the decades that followed. The association remained significant even after the researchers adjusted for age, sex, and established cardiovascular risk factors recorded within the cohorts.

The strongest relationship was observed for vascular dementia, a type of dementia caused by reduced blood flow to the brain. According to the researchers, this finding is consistent with the protein's known involvement in inflammatory and metabolic processes.

Genetic Analyses Supported the Findings

To determine whether GDF15 might play a more active role in dementia rather than simply reflecting existing disease, the team carried out a Mendelian randomization analysis. This approach uses naturally occurring genetic differences to explore whether a biological factor may contribute to disease risk.

Certain genetic variants are associated with lifelong increases in GDF15 levels. After analyzing genetic data from hundreds of thousands of individuals, the researchers found that people carrying these variants also faced a higher risk of developing dementia. Because genetic variants are determined at conception, this approach helps reduce the possibility that the association is explained by lifestyle factors or other illnesses.

Although these results strengthen the evidence for a potential biological role of GDF15, the researchers emphasize that genetic analyses alone cannot definitively establish cause and effect.

Brain Imaging and Spinal Fluid Offered Additional Evidence

The researchers also investigated smaller groups of participants who underwent brain imaging and cerebrospinal fluid testing. Cerebrospinal fluid surrounds both the brain and spinal cord and can provide important clues about neurological health.

Higher GDF15 concentrations in blood were linked to increased levels of the same protein in cerebrospinal fluid as well as lower brain volume on MRI scans.

However, GDF15 levels were not associated with amyloid beta, the protein that forms the characteristic plaques seen in Alzheimer's disease. Instead, the findings point toward possible roles in vascular injury, neuroinflammation, and more widespread brain atrophy.

Additional laboratory experiments using human immune cells provided further insight. Exposure to GDF15 altered immune pathways involved in inflammation and energy regulation, suggesting the protein could influence how the brain responds to long-term metabolic and vascular stress.

What the Findings Could Mean

GDF15 is already recognized as a stress-response protein that helps regulate excessive inflammation and has also been linked to limiting the spread of certain cancers. In dementia, however, the researchers suggest that this protective function could become detrimental if it suppresses immune activity needed to maintain healthy brain tissue.

If future studies confirm these findings, GDF15 could become a valuable blood biomarker for identifying people at elevated risk of dementia, particularly vascular dementia and other forms of cognitive decline associated with chronic inflammation. A routine blood test performed during midlife could one day help identify individuals who may benefit from earlier monitoring or preventive interventions.

The researchers caution that clinical use remains some way off. Further studies will be needed to establish appropriate threshold values, evaluate differences between populations, and determine whether targeting GDF15-related pathways can reduce the likelihood of developing dementia.

The findings also support broader efforts to detect dementia before symptoms appear, when measures such as controlling blood pressure, maintaining regular physical activity, following a healthy diet, and engaging in cognitive training are believed to offer the greatest opportunity to protect brain health. With more than 55 million people worldwide currently living with dementia, identifying reliable early biomarkers remains an important priority for researchers.

The study, published in Science Advances, provides further evidence that changes detectable in a simple blood sample may offer valuable insight into future brain health and is expected to encourage additional research into GDF15-based screening strategies and potential therapeutic approaches.