Highlights

Background: Compromised vascular health is increasingly linked to Alzheimer’s disease (AD) risk. Estimated pulse wave velocity (ePWV), derived from age and blood pressure, provides a practical, noninvasive index of vascular stiffness and overall vascular health. Older African Americans experience a disproportionate burden of vascular disease and AD. Genetic risk factors such as APOE-ε4 and ABCA7-80 (rs115550680) further increase AD susceptibility. However, whether these genetic risks influence vascular stiffness and how that may interact with AD pathology remains unknown, especially in African Americans.

Methods: A total of 145 older African Americans (mean age=71.18±6.83 years;110 women) were included. We examined the effects of both ABCA7-80 and APOE-ε4 genotypes on ePWV and plasma p-tau217. All regression models controlled for sex, education, pulse pressure, waist-to-hip ratio, global cognition, hypertension status, and APOE genotype (APOE genotype only used for ABCA7-80 regression models).

Results: ABCA7-80 risk allele carriers exhibited higher ePWV (F( 1 ,1 2 0 ) =8.16, p=.005, η ²ₚ=.064) and higher p-tau217 levels (F( 1 ,1 2 0 ) =30.11, p<.001, η ²ₚ=.201). APOE-ε4 allele carriers also showed higher p-tau217 levels (F( 1 ,1 2 8 ) =12.96, p<.001, η ²ₚ=.092). ABCA7-80 significantly moderated the relationship between ePWV and p-tau217 (F(1,118) = 4.40, p = .038, η²ₚ = .036), such that higher ePWV was associated with higher p-tau217 among ABCA7-80 risk carriers (β=0.52, t(118)=2.69, p=.008).

Conclusion: ABCA7-80, but not APOE-ε4, heightens susceptibility to tau-related effects of compromised vascular health among older African Americans. These findings identify a genetically vulnerable subgroup in whom vascular stiffness may disproportionately accelerate