A new study has found important clues about the roles age, sex, hormonal changes and genetics play in how certain biomarkers for dementia are expressed in the blood, according to a study published on April 16, 2025, online in Neurology®, the medical journal of the American Academy of Neurology.
“Blood tests that detect biomarkers for Alzheimer’s disease and other dementias are emerging and as these tests are further developed, they are becoming important tools for understanding and diagnosing these conditions,” said study author Hannah Stocker, PhD, MPH, of Heidelberg University in Germany. “Our findings provide valuable insights into how age, sex, genetics and hormonal changes during menopause are linked to three biomarkers believed to influence a person’s risk of dementia.”
Researchers analyzed data from a larger 17-year study, comparing 513 people who developed dementia during the study to 513 people who remained free of dementia during that time. The participants had an average age of 64 at the start of the study.
Researchers took blood samples from participants three times during the study to measure levels of three biomarkers: neurofilament light chain proteins, glial acidic proteins and phosphorylated tau 181. Neurofilament light chain proteins are found in the blood when nerve cells are injured or die. Glial acidic proteins are released when cells work to repair injury. Phosphorylated tau 181 is linked to the buildup of amyloid proteins in the body, which occurs in Alzheimer’s disease.
Researchers then compared levels of the biomarkers in people with and without dementia in the following ways: over time as people aged; in male and female participants; in people with and without a gene linked to Alzheimer’s; and in female participants before and after menopause.
After adjusting for age, sex, and APOEe4, a genetic biomarker that indicates a strong risk of Alzheimer’s disease, researchers found that an older age was tied to higher levels of all three markers.
For neurofilament light chain proteins, people age 75 had an average of 25 picograms per milliliter (pg/ml) compared to people age 50 with an average of 10 pg/ml. For glial acidic proteins, people age 75 had an average of 140 pg/ml compared to people age 50 with an average of 45 pg/ml. For phosphorylated tau 181, people age 75 had an average of two to three pg/ml compared to people age 50 with an average of 0.5 to 1.5 pg/ml.
Researchers also found that female participants had higher levels of glial acidic proteins, while male participants had higher levels of neurofilament light chain proteins.
In addition, they found people who had the APOEe4 gene had higher levels of tau and glial acidic proteins.
Lastly, the study found that female participants who had not yet gone through menopause had higher levels of glial acidic proteins, which Stocker noted may be due to having higher levels of sex hormones. Stocker said previous studies have found a link between sex hormones and neuroinflammation.
“Gaining a better understanding of these biomarkers will help improve our ability to test for dementia in the future with simple blood tests,” said Stocker. “Our research underscores the need to further explore these biomarkers, including during menopause, in the development of dementia.”
A limitation of the study was that participants were of European descent, so the results may not be the same for other populations.
The study was supported by the German Alzheimer Forschung Initiative.