journal articles
VASCULAR STIFFNESS PREDICTS PLASMA MARKERS OF NEURODEGENERATION AMONG OLDER AFRICAN AMERICANS
Miray Budak, Kevin S. Heffernan, Victoria Paruzel, Soodeh Moallemian, Bernadette A. Fausto, Nicholas Ashton, Henrik Zetterberg, Fanny M. Elahi, Mark A. Gluck
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.
CITATION:
Miray Budak ; Kevin S. Heffernan ; Victoria Paruzel ; Soodeh Moallemian ; Bernadette A. Fausto ; Nicholas Ashton ; Henrik Zetterberg ; Fanny M. Elahi ; Mark A. Gluck (2026): Vascular stiffness predicts plasma markers of neurodegeneration among older African Americans. The Journal of Prevention of Alzheimer’s Disease (JPAD). https://doi.org/10.1016/j.tjpad.2026.100523