Zagol-Ikapitte Irene A, Tabatabai Mohammad A, Wilus Derek M, Alcendor Donald J
Proteomics Laboratory, Mass Spectrometry Research Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
School of Global Health, Meharry Medical College, Nashville, TN 37208, USA.
J Clin Med. 2025 Jan 19;14(2):635. doi: 10.3390/jcm14020635.
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.
阿尔茨海默病（AD）及相关痴呆症（ADRD）对少数族裔的影响尤为严重。导致这种差异的生物学因素一直难以捉摸。此外，还需要用于早期检测AD的非侵入性生物标志物。内皮素-1（ET-1）是一种与脑血管疾病病理和神经元损伤相关的血管收缩因子，可能有助于更好地理解AD中的种族差异。作为一种调节平滑肌、内皮细胞和周细胞收缩的强效血管收缩肽，ET-1可能导致脑血管收缩，进而导致脑灌注不足；随着时间的推移，这可能会导致神经元损伤，从而促进AD的病理发展。ET-1系统作为AD种族差异驱动因素的作用需要进一步研究。在美国，西班牙裔/拉丁裔（H/L）族裔人群中ET-1失调的情况在很大程度上尚未得到研究。将ET-1失调与AD种族差异联系起来的遗传学也需要进一步研究。在本研究中，我们检测了人血浆中ET-1蛋白作为一种潜在生物标志物的作用，该标志物对于按年龄、种族和性别与AD的发展相关具有预测价值。我们使用定量质谱法检测了患有AD的非裔美国人（AA）和非西班牙裔白人（NHW）患者以及对照组的ET-1蛋白水平。在控制AD状态的情况下，按种族和性别分层后，采血时年龄与ET-1之间的偏相关性在女性AA中具有显著性（r = 0.385，P = 0.016）。当数据未分层但控制了AD状态时，采血时年龄与ET-1之间的偏相关性不显著（r = 0.108，P = 0.259）。基于血浆样本数量较少且没有来自患有AD的H/L个体的血浆样本，我们得出结论，在本研究中ET-1显然不是预测AD的重要因素，需要进行更大规模的研究来验证。
