Higher levels of a single blood protein, measured before the age of 55, were linked to a greater chance of developing dementia decades later. That is the finding from an international team that followed tens of thousands of people for 15 to 25 years. The protein is called GDF15, and it turns up in blood plasma.
For families across the region who watch parents and grandparents slow down, the idea of a warning sign that early is hard to ignore.
The team pulled together data from six independent cohort studies run in the US, the UK, Iceland and Japan. Each had blood sample readings for its participants and health records covering follow-up periods of 15 to 25 years. People with more GDF15 in their blood were more likely to be diagnosed with dementia in the decades that followed. The link was strongest for vascular dementia, which is caused by disruptions to the brain’s blood supply. The researchers tentatively tied that to the protein’s role in inflammation.
Earlier work had already connected higher GDF15 to dementia in later life. What is new is that the association holds for people below 55.
Numbers from midlife
A summary of the paper in Science Advances put figures on it. In midlife, people with higher GDF15 had roughly double the 20-year dementia risk, 7.5 percent against 3.9 percent. Each doubling of GDF15 raised risk by about 55 percent. Among people in their mid-to-late 70s, high levels were tied to a similar doubling of seven-year risk, 18.7 percent against 9.5 percent.
A marker, or a driver?
The team did not stop at the cohorts. They used a technique called Mendelian Randomization, which treats genetic patterns as stand-ins for something else, here high GDF15 in the blood. Across genetic datasets covering hundreds of thousands of people, those with variants linked to higher GDF15 also carried a higher risk of dementia. Because those genes are independent of lifestyle, environment and disease, the result hints that the protein may help drive dementia and not just flag it.
Smaller datasets with brain scans and cerebrospinal fluid samples added more. More GDF15 in the blood went with more in the fluid around the brain, and with brain shrinkage. It did not go with the amyloid beta clumps associated with Alzheimer’s. “We observed a strong correlation between plasma and CSF GDF15 levels, which is consistent with the possibility that circulating GDF15 crosses into the central nervous system,” the researchers wrote.
Lab tests on immune cells found GDF15 interfering with normal pathways for immune responses and energy management.
GDF15 normally helps keep the immune system in check, and studies have shown it can suppress cancer spread. The researchers suggest it may go too far in quietening the immune response when dementia is involved, leaving the brain vulnerable. They stress that much more work is needed to know for sure.
Testing for GDF15 is not part of routine care yet. In their paper, the researchers wrote that the findings “support circulating GDF15’s role as an early biomarker, particularly for vascular dementia and neuroinflammation,” and identify mechanisms by which it may drive dementia risk. Down the line, a blood measure could help doctors spot raised risk early and help scientists understand how the disease develops.
Sources
- One Specific Blood Protein Can Identify Dementia Risk Decades Before Diagnosis
- A Simple Blood Test Could Predict Dementia Risk 25 Years Early
- Researchers Identified A Blood Protein Linked To Future Dementia Risk
