# Relationships between blood pressure indicators and fluid biomarkers of brain aging in functionally intact older adults

## TL;DR

The study finds that higher pulse pressure is linked to increased brain aging biomarkers in older adults, suggesting blood pressure management could help prevent dementia.

## Contribution

This study is among the first to explore how specific blood pressure metrics relate to plasma biomarkers of brain aging in older adults.

## Key findings

- Higher pulse pressure was associated with increased levels of pTau181, NfL, and GFAP biomarkers.
- Elevated systolic blood pressure was linked to higher pTau181 levels.
- Females and APOE-ε4 carriers showed stronger associations between pulse pressure and biomarker levels.

## Abstract

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.

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.

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.

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.