Vascular dysfunction in health disparities – unraveling contributions to dementia and Alzheimer’s disease in South Alabama

Abstract

AbstractBackgroundIt is estimated that nearly 100,000 Alabamians have Alzheimer’s disease (AD). There is strong evidence that neurovascular uncoupling, cerebral blood flow reductions and dysregulation, and breakdown of the blood‐brain barrier (BBB), including the loss of pericytes, are early events in the AD pathophysiological cascade. Health, lifestyle, and socioeconomic risk factors across racial groups, and/or genetic risk factors, may account for this increased AD risk. Aged Black Americans have twice the risk of experiencing AD or other dementias compared to aged Whites. 26.8% of the Alabama population is Black American. Furthermore, over a million people in Alabama live in rural areas (USDA‐ERS), leading to healthcare professional shortages, and in designated medically underserved areas. Relatively little is known about the role of cerebrovascular mechanisms in the pathogenesis of dementia and AD and potential therapeutic targets within the neurovascular system, especially as they relate to health disparities. Thus, determining whether health disparities via vascular or genetic risk factors leads to neurovascular dysfunction and ultimately AD is essential.MethodBlood was collected from middle‐aged diverse individuals (67% Black, n = 12 and 33% White, n = 6, 61% of participants were female) that reside in the South Alabama vicinity. Plasma and buffy coat were used for biomarker assays and APOE genotyping, respectively. We identified APOE genotype using DNA extraction and PCR‐RFLP. We used MesoScale Discovery’s MESO QuickPlex SQ to quantify vascular biomarkers, tau and neurofilament light chain. Measurements of amyloid‐beta, inflammatory cytokines and other biomarkers are underway.Result67% of Blacks and 17% of Whites were APOE‐ε4 carriers. 39% of participants reside in designated rural or medically underserved areas. Blacks had increased bFGF, Flt‐1, VEGF‐C and tau. APOE‐ε4 carriers had increased VEGF‐C and tau. Females had increased Flt‐1 and VEGF‐A. Individuals residing in rural/medically underserved areas had increased bFGF.ConclusionWe observed a large % of APOE‐ε4 carriers in Black participants. The increase in VEGF‐C and tau in Black participants may have been provoked by APOE‐ε4 genotype. Vascular health and peripheral tau may play a crucial role in the development of AD. Improving modifiable vascular risk factors early with interventions such as exercise may help prevent AD.