Key result
ABCA7-80 risk allele moderates vascular stiffness link to elevated plasma p-tau217 in older Black adults.
Why the study?
Older African Americans experience disproportionate vascular disease and AD risk, and it is unknown how genetic risks like ABCA7-80 and APOE ε4 influence vascular stiffness and AD pathology in this population.
Does the ABCA7-80 risk allele moderate the relationship between vascular stiffness and tau-related neurodegeneration (p-tau217) in older African Americans?
Cross-Sectional (n=143)
No
Does the ABCA7-80 risk allele moderate the relationship between vascular stiffness and tau-related neurodegeneration (p-tau217) in older African Americans?
Effect estimate: β = 0.52
p-value: p=0.008
The ABCA7-80 risk allele identifies a genetically vulnerable subgroup of older African Americans in whom increased vascular stiffness may disproportionately accelerate Alzheimer's disease-related tau pathology.
ABCA7-80 may flag older African Americans with stronger vascular stiffness–p-tau217 links; hypothesis-generating and requires prospective validation.
Introduction Compromised vascular health is increasingly linked to Alzheimer's disease (AD) risk. Estimated pulse wave velocity (ePWV), derived from age and blood pressure, and provides a practical, non‐invasive 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 143 older African Americans (mean age = 71.10 ± 6.83 years; 109 women) were included. We examined the effects of both ABCA7‐80 and APOE ε4 genotypes on ePWV and plasma phosphorylated tau 217 (p‐tau217). All regression models controlled for sex, education, pulse pressure, waist‐to‐hip ratio, global cognitive status, hypertension status, and APOE genotype (APOE genotype only used for ABCA7‐80 regression models). Results ABCA7‐80 risk allele carriers exhibited higher ePWV ( F (1,130) = 8.16, p = 0.005, η 2 p = 0.064) and higher p‐tau217 levels ( F (1,130) = 30.11, p < 0.001, η 2 p = 0.201). APOE ε4 allele carriers also showed higher p‐tau217 levels ( F (1,131) = 12.96, p < 0.001, η 2 p = 0.092). ABCA7‐80 significantly moderated the relationship between ePWV and p‐tau217 (F (1,130) = 6.58, p < 0.001), such that higher ePWV was associated with higher p‐tau217 among ABCA7‐80 risk carriers ( β = 0.52, t (130) = 2.69, p = 0.008). Discussion ABCA7‐80 risk, but not APOE ε4, heightens susceptibility to the tau‐related effects of compromised vascular health among older African Americans. These findings identify a genetically vulnerable subgroup in which vascular stiffness may disproportionately accelerate AD‐related tau pathology and highlight vascular health as a modifiable target for reducing AD risk in African Americans.
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Budak et al. (2026) conducted a cross-sectional in Alzheimer's disease risk (n=143). ABCA7-80 risk allele vs. Non-risk allele carriers was evaluated on Moderation of the relationship between estimated pulse wave velocity (ePWV) and plasma p-tau217 (β = 0.52, p=0.008). The ABCA7-80 risk allele significantly moderated the relationship between vascular stiffness and plasma p-tau217 in older African Americans, with a strong association seen only in risk carriers (β = 0.52, p = 0.008).
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