Hall James R, Petersen Melissa, Johnson Leigh, O'Bryant Sid E
Institute for Translational Research, University of North Texas Health Science Center, Fort Worth, TX, United States.
Department of Family Medicine, University of North Texas Health Science Center, Fort Worth, TX, United States.
Front Neurol. 2022 Aug 18;13:871947. doi: 10.3389/fneur.2022.871947. eCollection 2022.
Due to their low cost, less invasive nature, and ready availability, plasma biomarkers of Alzheimer's disease have been proposed as one-time screening tools for clinical trials and research. The impact of ethnoracial factors on these biomarkers has received little attention. The current cross-sectional study investigated the levels of Aβ, Aβ, total tau (t tau), and neurofilament light (NfL) across diagnoses for each of the three major ethnoracial groups in the United States in a community-based cohort of older adults.
A total of 1,862 participants (852 Mexican Americans (MAs); 775 non-Hispanic Whites (NHWs), and 235 African Americans (AAs)) drawn from The Health & Aging Brain Study-Health Disparities (HABS-HD) study were included. Diagnoses were assigned using an algorithm (decision tree) verified by consensus review. Plasma samples were assayed using Simoa technology. Levels of each biomarker were compared for the three ethnoracial groups across cognitive diagnoses using ANOVA covarying sex and age.
Significant differences were found across the groups at each level of cognitive impairment. Cognitively unimpaired (CU) AA had significantly lower levels of each of the biomarkers than cognitively unimpaired MA or NHW and NHW had higher levels of Aβ, and NfL than the other two groups. MA had higher t tau than AA or NHW. Mild cognitive impairment (MCI) group NHW had the highest levels on all the biomarkers and AA had the lowest. NHW and MA have higher levels of Aβ, Aβ, and t tau there was no difference between the groups for Aβ. NHW had significantly higher levels of Aβ, t tau, and NfL than AA. AA had a higher Aβ/Aβ ratio than either NHW or MA for CU MCI.
The use of plasma biomarkers of cognitive decline is promising given their advantages over other biomarkers such as CSF and imaging but as the current research shows, ethnoracial differences must be considered to enhance accuracy and utility. Developing ethnoracial-specific cut points and establishing normative ranges by assay platform for each of the biomarkers are needed. Longitudinal research to assess changes in biomarkers during a cognitive decline is ongoing.
由于成本低、侵入性小且易于获取，阿尔茨海默病的血浆生物标志物已被提议作为临床试验和研究的一次性筛查工具。种族因素对这些生物标志物的影响很少受到关注。当前的横断面研究调查了美国三个主要种族群体中，基于社区的老年人群队列中，各诊断组的淀粉样蛋白β（Aβ）、总tau蛋白（t tau）和神经丝轻链（NfL）水平。
纳入了来自健康与衰老大脑研究-健康差异（HABS-HD）研究的总共1862名参与者（852名墨西哥裔美国人（MAs）；775名非西班牙裔白人（NHWs）和235名非裔美国人（AAs））。诊断通过经共识审查验证的算法（决策树）进行。血浆样本使用单分子阵列技术（Simoa）进行检测。使用协方差分析性别和年龄，比较了三个种族群体在不同认知诊断下各生物标志物的水平。
在每个认知障碍水平上，各群体之间均发现了显著差异。认知未受损（CU）的非裔美国人的每种生物标志物水平均显著低于认知未受损的墨西哥裔美国人或非西班牙裔白人，且非西班牙裔白人的Aβ和NfL水平高于其他两组。墨西哥裔美国人的t tau水平高于非裔美国人或非西班牙裔白人。轻度认知障碍（MCI）组中，非西班牙裔白人在所有生物标志物上的水平最高，非裔美国人最低。非西班牙裔白人和墨西哥裔美国人的Aβ、Aβ和t tau水平较高，各群体之间的Aβ无差异。非西班牙裔白人的Aβ、t tau和NfL水平显著高于非裔美国人。在认知未受损和轻度认知障碍的非裔美国人中，Aβ/Aβ比值高于非西班牙裔白人或墨西哥裔美国人。
鉴于血浆认知衰退生物标志物相对于其他生物标志物（如脑脊液和影像学）具有优势，其应用前景广阔，但正如当前研究所显示的，必须考虑种族差异以提高准确性和实用性。需要针对每个生物标志物开发种族特异性的切点，并通过检测平台建立正常范围。正在进行纵向研究以评估认知衰退期间生物标志物的变化。
