Plasma Endothelin-1 Levels: Non-Predictors of Alzheimer's Disease Reveal Age Correlation in African American Women.

Alzheimer's disease (AD) and related dementias (ADRD) disproportionately impact racial and ethnic minorities. Contributing biological factors that explain this disparity have been elusive. Moreover, non-invasive biomarkers for early detection of AD are needed. Endothelin-1 (ET-1), a vasoconstrictive factor linked to cerebral vascular disease pathology and neuronal injury, could provide insights to better understand racial disparities in AD. As a potent vasoconstrictive peptide that regulates contractions in smooth muscle, endothelial cells, and pericytes, ET-1 may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, this may result in neuronal injury, contributing to the pathology of AD. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. In the United States (U.S.), ET-1 dysregulation in Hispanic/Latinx (H/L) ethnic populations has largely been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also require further investigation. In this study, we examined the role of the ET-1 protein in human plasma as a potential biomarker with predictive value for correlating with the development of AD by age, race, and sex. We examined ET-1 protein levels using quantitative mass spectrometry in AA and NHW patients with AD, along with controls. A partial correlation between age at draw and ET-1, stratified by race and sex, while controlling for AD status, was significant for female AAs (r = 0.385, = 0.016). When the data were not stratified but controlled for AD status, the partial correlation between age at draw and ET-1 was not significant (r = 0.108, = 0.259). Based on the small number of plasma specimens and no plasma specimens from H/L individuals with AD, we conclude that ET-1 was clearly not a significant factor in predicting AD in this study and will require a larger scale study for validation.