Age and sex shape Alzheimer’s blood biomarkers, study finds

In a 17-year-old German cohort study, researchers discovered age, Apoe ε4 status and especially female sex an important role in determining the levels of Alzheimer’s-related blood biomarkers, who offer new insights into how these risk factors form the disease progression.

Study: Association of non-modifiable risk factors with Alzheimer’s Disease Blood Biomarkers in community-lying adults in the Esther study. Image Credit: Kateryna Kon / Shutterstock.com

A recent studying in the Neurology Journal investigates the Associations between dementia-related blood biiomarker mirrors and non-modifiable risk factors.

Well -known risk factors for dementia

P-TAU181 is an established biomarker of the pathology of Alzheimer’s disease (AD) that can predict tau and amyloid β (AP) pathologies. In comparison with other biomarkers, serum levels of neuro-movie lamp (NFL) chains can indicate that non-disease-specific neurodegeneration can be used to follow disease progression.

The expression of glial fibrillary acid protein (GFAP) can be used to distract astrocyte activation levels and can, as a result, support the early detection of Alzheimer’s disease (AD). To date, few studies have investigated the potential usefulness of measuring NFL and GFAP levels in supporting the diagnosis and monitoring of AD. Moreover, it remains unclear how these biomarker mirrors can be influenced by the presence of non-modifiable factors such as age, gender, apolipoprotein E4 (Apoee4) Levels and Menopause.

About the study

The current study is investigating the potential associations between non-modifiable risk factors, including age, gender, and Apoe ε4 Status and dementia-related blood biomarkers from P-TAU181, NFL and GFAP. The study cohort consisted of community -dwelling adults aged 50 to 75 without a history of dementia.

All participants in the study were monitored for 17 years as part of the German Esther research. The effects of menopause on biomarker mirrors were also investigated.

From the first Esther-Steek test of 9,940 people, a nested case-control study of 1,026 participants was carried out for the current analysis. P-TAU181, NFL and GFAP measurements were obtained during follow-up visits of the start, eight years and 11 years. Cross-sectional and longitudinal regression analyzes were also performed to further analyze any observed associations.

Study findings

The average age of the research cohort was 64 years, with 54% of the participants being female. The median age at the diagnosis of dementia was 78 years.

About 39% of the participants in the study in the Incident Dementia Group was Apoe ε4 Carriers. In comparison with the rest of the research cohort, 26% of the participants were never diagnosed with dementia during the study period. The average biomarker mirrors at the start were 1.78, 17.4 and 104.2 pg/ml for P-TAU181, NFL and GFAP respectively.

In the transversal analyzes, NFL and GFAP showed a stronger correlation with the age at the start than P-TAU181 levels. Women also had significantly lower levels of NFL and considerably higher GFAP levels at the start.

Among the entire levels of the study cohort, NFL, GFAP and P-TAU181 were significantly associated with the age at the start, after checking for sex and Apoe ε4 Status. P-TAU181 levels were not associated with sex.

Significantly higher levels of both P-TAU181 and GFAP were detected in Apoe E4 Carriers. Apoee4 Carriers that developed dementia continued to show important associations with P-TAU181, GFAP and NFL levels; However, these associations were not observed at Apoee4 Carriers who have never been diagnosed with dementia.

Age, gender and Apoe ε4 Carrier status contributes to approximately 2% of the variance in P-TAU181, 17% in NFL and 16% in GFAP levels, with age in these cases being the primary contributing factor. After adjusting age, gender and Apoee4 Status, the annual rates of P-TAU181, NFL and GFAP change were 0.14, 0.93 and 5.65 pg/ml respectively.

NFL and GFAP levels increased faster in participants in the study between 65 and 75 at the start. This relationship between older age and P-TAU181 levels was not observed.

The speed of increasing the GFAP levels was considerably faster with older participants in the incident dementia group. Under checks, the NFL levels increased considerably faster than those between 65 and 75 years old.

GFAP can record earlier biological processes related to Apoee4 Status, which can be important in the future risk assessment of dementia. “

Women were associated with a faster rise in GFAP levels. In the control group, Apoe ε4 Carriers experienced considerably faster percentages of increasing GFAP levels. After adjusting the age and Apoee4 Status, only GFAP levels were significantly associated with the menopause.

Conclusions

Women, especially premenopausal women, showed considerably higher GFAP levels at the start and a faster increase in GFAP levels over time compared to male participants in the study. These sex differences can be due to increased neuro inflammation in women, as well as sex-dependent astrocytic reactions to hormones. Nevertheless, further research is needed to clarify the mechanisms that underlie the association between GFAP levels and female gender.

Apoee4 Status can also be involved in astrocytic reactions. However, additional studies are needed to clarify the role of this genotype when maintaining NFL and GFAP levels.

The research results confirm that age and sex-specific reference values ​​are required for P-TAU181, NFL and GFAP blood levels. Although these strategies can facilitate the use of these biomarkers for diagnostic purposes of dementia, future studies must be carried out to confirm whether sex -specific differences in the brain contribute to biomarker levels in the blood.