Dysregulation of Endothelin-1: Implications for Health Disparities in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) and related dementias disproportionately impact racial and ethnic minorities. The racial and ethnic disparities in AD could be explained by differences in cerebral vascular disease pathology. Endothelin-1 (ET-1) is a potent vasoconstrictive peptide that regulates smooth muscle, endothelial cell, and pericyte contractions that may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, ET-1 may result in neuronal injury contributing to the pathology of AD. Upregulation of the ET-1 system has been observed in African Americans when compared with non-Hispanic Whites. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. Targeting of the ET-1 system as a therapeutic intervention that could impact AD progression also needs further study. Dysregulation of ET-1 in Hispanic/Latino populations largely have been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also needs further investigation. In this review, I examine how AD effects underserved minority populations and how dysregulation of the ET-1 system specifically predisposes ethnic minorities to AD. In addition, I examine the molecular interactions of the ET-1 system and amyloid beta, the role the ET-1 system in neurodegeneration, potential therapeutics for ET-1 dysregulation, and the impact on AD progression.