Association of Alzheimer's disease blood-based biomarkers and visit-to-visit blood pressure variability: The HABS-HD study

Abstract

Background

The interplay between Alzheimer's disease (AD) and the cardiovascular system remains poorly understood. While vascular factors influencing AD have been studied, whether AD pathology conversely affects blood pressure regulation is unclear.

Objective

This study investigated whether baseline plasma AD biomarkers predict subsequent visit-to-visit blood pressure variability (BPV).

Methods

This prospective analysis included 470 community-based older adults from the Health and Aging Brain Study-Health Disparities (HABS-HD) cohort. Multiple linear regression models separately assessed associations between each baseline plasma AD biomarker (Aβ_42/40 ratio, total tau, p-tau181, NfL) and follow-up BPV, with progressive adjustments for demographics, clinical diagnosis, cardiovascular risk factors, and mean blood pressure. In fully adjusted models, all plasma AD biomarkers were included simultaneously to adjust for potential mutual confounding and identify independent associations. Subgroup and sensitivity analyses were conducted.

Results

In fully adjusted models, total tau remained independently associated with higher systolic blood pressure variability (β = 3.94, 95%CI: 1.00–6.87, p = 0.009). These associations were particularly prominent in males (β = 5.80, 95% CI: 1.66–9.95, p = 0.007), non-Hispanic White (β = 4.00, 95% CI: 0.12–7.88, p = 0.044), cognitively unimpaired individuals (β = 4.42, 95% CI: 1.14–7.70, p = 0.009), APOE ε4 non-carriers (β = 4.91, 95% CI: 1.42–7.70, p = 0.009), and individuals not using antihypertensive medication (β = 4.29, 95% CI: 0.71–7.87, p = 0.020). Sensitivity analyses confirmed robustness of findings.

Conclusions

Plasma total tau independently predicts BPV, especially during pre-clinical AD stages. This finding reveals an important connection between AD pathology and vascular dysregulation, supporting the paradigm of AD as a systemic disorder and providing new directions for early risk identification and intervention.