Sex and age play key roles in dementia biomarker levels

A new study has found important indications about the age of roles, gender, hormonal changes and genetics play in how certain biomarkers are expressed for dementia 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 dementies are on the rise and as these tests are further developed, they become important tools for understanding and diagnosing these disorders. Our findings offer valuable insights into how age, gender, genetics and hormonal changes during menopause are linked to three biomarkers that are believed to influence the risk of dementia of a person. “

Hannah Stocker, PhD, MPH, Study author Van Heidelberg University, Germany

Researchers analyzed data from a larger study of 17 years, in which 513 people were compared who developed dementia during the study with 513 people who remained free from dementia at the time. The participants had an average age of 64 years at the start of the study.

During the study, researchers took blood samples three times to measure the levels of three biomarkers: Neuroilament light chain proteins, glial acid proteins and fosphorylated tau 181. Neuroilament light proteins are found in the blood when nerve cells are injured or die. Glial acid proteins are released when cells work to repair injury. Fosphorylored Tau 181 is linked to the structure of amyloid proteins in the body, which occurs in Alzheimer’s disease.

Researchers then compared levels of biomarkers in people with and without dementia in the following ways: over time as people of age; with male and female participants; In people with and without a gene linked to Alzheimer’s; And with female participants before and after the menopause.

After correction for age, gender and apoee4, a genetic biomarker who indicates a strong risk of Alzheimer’s disease, researchers discovered that an older age was bound by higher levels of all three markers.

For proteins of the light chain of Neurophilament, people had 75 years on average 25 picograms per milliliters (PG/ml) compared to people aged 50 with an average of 10 pg/ml. For glial acid proteins, people had an average of 140 pg/ml for 75 years compared to people aged 50 with an average of 45 pg/ml. For fosphorylated TAU 181, people had 75 years on average two to three pg/ml compared to people aged 50 with an average of 0.5 to 1.5 pg/ml.

Researchers also discovered that female participants had higher levels of glial sour proteins, while male participants had higher levels of neuroilament light chain proteins.

Moreover, they discovered that people with the Apoee4 gene higher levels of tau and glial sour proteins had.

Finally, the study showed that female participants who had not yet passed the menopause had higher levels of glial acid proteins, of which Stocker noticed, may be due to having higher levels of sex hormones. Stocker said that earlier studies have found a connection between sex hormones and neuro inflammation.

“Obtaining a better understanding of these biomarkers will help our ability to test dementia with simple blood tests in the future,” said Stocker. “Our research underlines the need to further explore these biomarkers, including during the menopause, in the development of dementia.”

A limitation of the research 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.