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The journal of prevention of Alzheimer's disease
Published

Vascular stiffness predicts plasma markers of neurodegeneration among older African Americans

Authors

Miray Budak, Kevin S Heffernan, Victoria Paruzel, Soodeh Moallemian, Bernadette A Fausto, Nicholas Ashton, Henrik Zetterberg, Fanny M Elahi, Mark A Gluck

Abstract

J Prev Alzheimers Dis. 2026 Feb 27;13(4):100523. doi: 10.1016/j.tjpad.2026.100523. Online ahead of print.

ABSTRACT

BACKGROUND: 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.

OBJECTIVES: To examine associations between vascular stiffness and plasma biomarkers of AD-related neurodegeneration in older African Americans.

DESIGN: Cross-sectional observational study.

SETTING: Community-based aging cohort study conducted at an academic research center.

PARTICIPANTS: A total of 145 cognitively unimpaired older African Americans (mean age=71.18±6.83 years; 110 women).

MEASUREMENTS: 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.

RESULTS: Higher ePWV was significantly associated with higher plasma concentrations of p-tau217 (β=0.34, p=.006), GFAP (β=0.55, p<.001), and NfL (β=0.52, p<.001), but not with p-tau231 and Aβ42/40 (p>.05).

CONCLUSIONS: 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.

PMID:41763008 | DOI:10.1016/j.tjpad.2026.100523

UK DRI Authors

Profile picture of Henrik Zetterberg

Prof Henrik Zetterberg

Group Leader

Pioneering the development of fluid biomarkers for dementia

Prof Henrik Zetterberg