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A recent investigation has unveiled significant insights regarding the interaction of age, sex, hormonal fluctuations, and genetics with various blood biomarkers linked to dementia. This research, published on April 16, 2025, in Neurology®, the official journal of the American Academy of Neurology, contributes to the growing body of evidence related to the diagnosis and understanding of dementia.
According to Hannah Stocker, PhD, MPH, from Heidelberg University in Germany, “Emerging blood tests that identify biomarkers for Alzheimer’s disease and other forms of dementia are becoming increasingly vital for diagnosing these conditions.” She added, “Our research reveals essential connections between demographic factors such as age, sex, genetic predisposition, and the hormonal changes experienced during menopause, and their association with three specific biomarkers that may indicate an individual’s risk for dementia.”
The research team evaluated data from a comprehensive 17-year-long study, analyzing 1,026 participants, of which 513 developed dementia while the remaining remained dementia-free. The average age at the study’s commencement was 64 years.
Blood samples were collected from participants at three different intervals throughout the study to measure the levels of three distinct biomarkers: neurofilament light chain proteins, glial acidic proteins, and phosphorylated tau 181. Neurofilament light chain proteins appear in the bloodstream when nerve cells sustain injury or die, while glial acidic proteins are indicators of cellular repair processes. Phosphorylated tau 181 is associated with the accumulation of amyloid proteins, a hallmark of Alzheimer’s disease.
In their analysis, researchers looked at how the levels of these biomarkers varied over time, across different sexes, among individuals with and without a genetic variant linked to Alzheimer’s, and in women before and after menopause.
After adjusting for factors like age, sex, and the presence of the APOEe4 gene—a significant genetic risk factor for Alzheimer’s—the study revealed a correlation between aging and increased levels of all three biomarkers. For instance, individuals aged 75 had an average level of 25 picograms per milliliter (pg/ml) of neurofilament light chain proteins, starkly higher than the 10 pg/ml average recorded for those aged 50. Likewise, glial acidic proteins demonstrated averages of 140 pg/ml and 45 pg/ml in the respective age groups, along with phosphorylated tau 181 showing averages of two to three pg/ml for the older group compared to 0.5 to 1.5 pg/ml for the younger cohort.
Notably, the study found that female participants exhibited elevated levels of glial acidic proteins, whereas male participants had higher concentrations of neurofilament light chain proteins. Additionally, individuals carrying the APOEe4 gene displayed increased levels of tau and glial acidic proteins.
The findings also indicated that premenopausal women tended to show higher levels of glial acidic proteins, a situation that Stocker attributed potentially to elevated sex hormone levels. Previous studies have suggested a connection between sex hormones and neuroinflammation, which could influence the results.
Stocker emphasized that improved comprehension of these biomarkers promises to enhance future dementia testing capabilities through straightforward blood tests. “Our findings highlight the necessity for further investigation into these biomarkers, especially during menopause, as they play a crucial role in dementia development,” she stated.
However, it is important to note that the study is limited by its demographic focus, primarily comprising participants of European descent, which may affect the generalizability of the results to other populations.
This research was financed by the German Alzheimer Forschung Initiative, reinforcing the ongoing commitment to understanding the complexities of dementia and its risk factors.
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