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Relationships between blood pressure indicators and fluid biomarkers of brain aging in functionally intact older
Anna M VandeBunte1, Bailey L Ortiz1, Emily W Paolillo1
1University of California, San Francisco.
Insights
Elevated pulse pressure is linked to higher levels of dementia-related biomarkers, including those for Alzheimer's disease and neurodegeneration. Managing blood pressure, especially pulse pressure, is crucial for brain health and reducing dementia risk.
Area of Science:
- Neuroscience
- Cardiovascular Health
- Biomarker Research
Background:
- Cardiovascular health significantly influences dementia risk, with high blood pressure being a key factor in brain aging.
- Blood biomarkers (pTau181, Aβ42/40, NfL, GFAP) aid dementia understanding, but their link to specific blood pressure metrics needs further exploration for personalized prevention.
- This study investigates the association between various blood pressure metrics and plasma biomarkers related to neurodegeneration and Alzheimer's disease.
Purpose of the Study:
- To examine the relationship between different blood pressure metrics (diastolic, systolic, pulse pressure) and plasma biomarkers.
- To assess how these relationships vary by sex, age, and APOE-ε4 status.
- To understand the implications for personalized dementia prevention strategies.
Main Methods:
- 109 cognitively intact older adults underwent blood draws for plasma biomarker analysis (pTau181, Aβ42/40, NfL, GFAP).
- In-lab blood pressure was quantified, including diastolic, systolic, and pulse pressure.
- Regression and interaction models were used to analyze biomarker levels as a function of blood pressure metrics, adjusting for covariates.
Main Results:
- Higher pulse pressure correlated with increased levels of pTau181, NfL, and GFAP, but not Aβ42/40.
- Higher systolic blood pressure was associated with elevated pTau181; diastolic blood pressure showed no significant association.
- Elevated pulse pressure showed a stronger link to higher GFAP in females and lower Aβ42/40 in APOE-ε4 carriers.
Conclusions:
- Elevated pulse pressure and systolic blood pressure are associated with increased markers of Alzheimer's disease and neurodegeneration.
- These findings highlight the importance of blood pressure management, particularly pulse pressure, for dementia risk reduction.
- Integrating cardiovascular health data with biomarkers can enhance personalized dementia prevention and management.
Background:
Dementia risk is significantly shaped by cardiovascular health, with elevated blood pressure emerging as a key risk factor for adverse brain aging. Blood biomarkers such as pTau181, Aβ42/40, NfL, and GFAP have improved our understanding of dementia pathophysiology, however, few studies have explored how specific blood pressure metrics relate to biomarker levels, which could inform personalized dementia prevention strategies as these biomarkers move into clinic. We examined how different blood pressure metrics associated with molecular markers of astrocytic activation (GFAP), neuronal axon breakdown (NfL), and Alzheimer's disease pathobiology (pTau181, Aβ42/40) in plasma.
Methods:
109 functionally intact (Clinical Dementia Rating Scale=0) older adults completed blood draws with plasma assayed for Aβ42/40, GFAP, NfL, and pTau181 (Quanterix Simoa) and in-lab blood pressure quantification. Blood pressure metrics included diastolic blood pressure, systolic blood pressure, and pulse pressure (systolic minus diastolic). Separate regression models evaluated plasma biomarkers as a function of each blood pressure metric, adjusting for age and biological sex. Interaction models tested whether relationships between blood pressure metrics and plasma biomarkers differed by sex, age, or APOE-ε4 status.
Results:
With the exception of Aβ42/40, higher pulse pressure related to higher levels of all plasma biomarkers examined (pTau181, NfL, GFAP). Additionally, higher systolic blood pressure related to higher pTau181, while diastolic blood pressure did not meaningfully associate with any biomarker. Interaction models revealed a significantly stronger relationship between elevated pulse pressure and higher GFAP concentrations in females compared to males, as well as a significantly stronger association between elevated pulse pressure and lower Aβ42/40 plasma concentrations in APOE-ε4 carriers compared to non-carriers.
Conclusions:
Our findings suggest that elevated pulse pressure, and to a lesser extent systolic blood pressure, are associated with increased Alzheimer's disease and neurodegenerative (axonal and astrocytic health) biology among typically aging adults. These associations underscore the importance of blood pressure management, particularly pulse pressure, for reducing dementia risk. Cardiovascular health may be incorporated with biomarkers to further personalize dementia prevention and management strategies.
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