Vascular stiffness predicts plasma markers of neurodegeneration among older African Americans

• 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 <.001), and NfL ( β =0.52, p <.001), but not with p-tau231 and Aβ42/40 ( 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.