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March 2, 2026The Journal of Prevention of Alzheimer s Disease2 citationsOpen Access

Vascular stiffness predicts plasma markers of neurodegeneration among older African Americans

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MBMİRAY BUDAKKHKevin S. HeffernanVPVictoria Paruzel

Key Result

Higher ePWV was significantly associated with increased plasma p-tau217 (β=0.34, p=.006), GFAP (β=0.55, p<.001), and NfL (β=0.52, p<.001) in older African Americans.

Key Points

  • This study examines the relationship between vascular stiffness and plasma biomarkers of neurodegeneration in older African Americans.
  • Cross-sectional observational study design
  • Examined 145 cognitively unimpaired older African Americans
  • Calculated estimated pulse wave velocity (ePWV) as a measure of vascular stiffness
  • Measured plasma biomarkers including p-tau217, GFAP, and NfL
  • Used multivariable regression models adjusted for multiple factors
  • Higher ePWV is significantly associated with increased levels of p-tau217, GFAP, and NfL
  • ePWV was not associated with p-tau231 and Aβ42/40
  • Findings suggest that vascular stiffness may signal early neurodegenerative processes
  • Indicates that vascular health could be a modifiable risk factor for Alzheimer’s disease

Structured PICO

Does higher estimated pulse wave velocity (ePWV) predict higher circulating levels of plasma biomarkers of neurodegeneration in cognitively unimpaired older African Americans?

P
Population
145 cognitively unimpaired older African Americans (mean age=71.18±6.83 years; 110 women) from a community-based aging cohort study
I
Intervention
Higher estimated pulse wave velocity (ePWV) derived from age and blood pressure
O
Outcome
Plasma concentrations of p-tau217, p-tau231, GFAP, NfL, and Aβ42/40 ratiosurrogate

Higher estimated pulse wave velocity, a marker of vascular stiffness, is associated with elevated plasma biomarkers of neurodegeneration (p-tau217, GFAP, NfL) in cognitively unimpaired older African Americans.

Abstract

• ePWV indexes vascular stiffness, a key component of vascular health. • Higher ePWV predicts higher circulating levels of plasma p-tau217, GFAP, and NfL. • Vascular stiffness may signal early neurodegenerative biomarker burden. • ePWV is a scalable, low-cost marker of AD-related risk in older African Americans. Vascular health is a critical and potentially modifiable determinant of Alzheimer’s disease (AD) risk, yet its contribution to early neurodegenerative processes remains incompletely understood, particularly among African Americans, who experience a disproportionate AD burden. Estimated pulse wave velocity (ePWV), derived from age and blood pressure, provides a scalable index of vascular stiffness. To examine associations between vascular stiffness and plasma biomarkers of AD-related neurodegeneration in older African Americans. Cross-sectional observational study. Community-based aging cohort study conducted at an academic research center. A total of 145 cognitively unimpaired older African Americans (mean age=71.18±6.83 years; 110 women). ePWV was calculated using validated equations based on age and blood pressure. Plasma biomarkers included phosphorylated tau217 (p-tau217; N=145), phosphorylated tau231 (p-tau231; N=126), glial fibrillary acidic protein (GFAP; N=126), neurofilament light chain (NfL; N=126), and amyloid-β42/40 ratio (Aβ42/40; N=126). Multivariable regression models adjusted for sex, education, pulse pressure, waist-to-hip ratio, global cognition, and hypertension status. Higher ePWV was significantly associated with higher plasma concentrations of p-tau217 ( β =0.34, p =.006), GFAP ( β =0.55, p .05). Greater vascular stiffness, indexed by elevated ePWV, was associated with circulating markers of tau-related neurodegeneration, astrocytic activation, and axonal injury in cognitively unimpaired older African Americans. The absence of association with p-tau231 and Aβ42/40 suggests preferential effects on neurovascular damage and later tau-related processes, but no primary effect on biomarkers related to Aβ pathology, still highlighting vascular health as a modifiable target for AD prevention.

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Cite This Study

BUDAK et al. (2026) studied this question. Higher ePWV was significantly associated with increased plasma p-tau217 (β=0.34, p=.006), GFAP (β=0.55, p<.001), and NfL (β=0.52, p<.001) in older African Americans.

synapsesocial.com/papers/69a52d9af1e85e5c73bf08b6https://doi.org/10.1016/j.tjpad.2026.100523
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