ABCA7-80 moderates vascular stiffness-p-tau217 association in older African Americans

Area of Science:

• Neuroscience and Genetics
• Cardiovascular Health and Aging

Background:

• Compromised vascular health is a growing risk factor for Alzheimer's disease (AD).
• Older African Americans face a higher burden of vascular disease and AD.
• Genetic factors like APOE ε4 and ABCA7-80 influence AD susceptibility, but their impact on vascular health and AD pathology is unclear in this demographic.

Purpose of the Study:

• To investigate the effects of ABCA7-80 and APOE ε4 genotypes on vascular stiffness (estimated pulse wave velocity, ePWV) and AD pathology marker (plasma phosphorylated tau 217, p-tau217).
• To examine the interaction between genetic risk factors and vascular health in relation to AD pathology among older African Americans.

Main Methods:

• Study included 143 older African Americans.
• Examined the association of ABCA7-80 and APOE ε4 genotypes with ePWV and p-tau217 levels.
• Regression models controlled for demographic, clinical, and genetic covariates.

Main Results:

• Carriers of the ABCA7-80 risk allele showed significantly higher ePWV and p-tau217 levels.
• APOE ε4 carriers also exhibited higher p-tau217 levels.
• ABCA7-80 genotype significantly moderated the association between ePWV and p-tau217, with higher ePWV linked to higher p-tau217 in ABCA7-80 risk carriers.

Conclusions:

• The ABCA7-80 risk allele, unlike APOE ε4, heightens susceptibility to tau-related effects of poor vascular health in older African Americans.
• This identifies a specific genetic subgroup where vascular stiffness may accelerate AD tau pathology.
• Maintaining vascular health is a potential modifiable target for reducing AD risk in this population.