Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer's Disease Cohorts of Diverse Genetic Ancestries.
Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer's Disease Cohorts of Diverse Genetic Ancestries.
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Tau 和淀粉样蛋白血浆生物标志物在不同遗传祖先的阿尔茨海默病队列中的普遍性。
DOI：
10.1101/2024.04.10.24305617
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
B
中科院分区：
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作者：
Griswold,AnthonyJ;Rajabli,Farid;Gu,Tianjie;Arvizu,Jamie;Golightly,CharlesG;Whitehead,PatriceL;Hamilton-Nelson,KaraL;Adams,LarryD;Sanchez,JoseJavier;Mena,PedroR;Starks,TakiyahD;Illanes-Manrique,Maryenela;Silva,Concepcion;B
血浆tau蛋白磷酸化苏氨酸181（pTau 181）和β淀粉样蛋白（Aβ）是阿尔茨海默病（Alzheimer disease，AD）鉴别诊断和临床前检测的生物标志物。鉴于不同人群中AD风险的差异，现有生物标志物数据的普遍性尚不确定。METHODSIn 2086个不同遗传血统的个体（非洲裔美国人，加勒比海西班牙裔和秘鲁人），我们测量了血浆pTau 181和Aβ42/Aβ40。评估队列和临床诊断组之间生物标志物的差异以及两种生物标志物的潜在区分性能。较高水平的pTau 181与AD相关，而Aβ42/Aβ40差异极小。相应地，pTau 181的预测价值高于Aβ42/Aβ40;然而，曲线下的面积在队列之间存在差异。结论：pTau 181作为临床AD的血浆生物标志物在遗传祖先中具有普遍性，但其预测价值可能会有所不同。结合来自不同个体的基因组和生物标志物数据将增加对遗传风险的理解并完善临床诊断。生物标志物水平在不同的队列中是一致的。在所有队列中，AD患者的血浆磷酸化tau蛋白水平较高。不同队列中的血浆生物标志物发现在很大程度上概括了现有的欧洲研究。
INTRODUCTIONPlasma phosphorylated threonine 181 of tau (pTau181) and amyloid beta (Aβ) are biomarkers for differential diagnosis and preclinical detection of Alzheimer disease (AD). Given differences in AD risk across diverse populations, the generalizability of existing biomarker data is not assured.METHODSIn 2086 individuals of diverse genetic ancestries (African American, Caribbean Hispanic, and Peruvian), we measured plasma pTau181 and Aβ42/Aβ40. Differences in biomarkers between cohorts and clinical diagnosis groups and the potential discriminative performance of the two biomarkers were assessed.RESULTSpTau181 and Aβ42/Aβ40 were consistent across cohorts. Higher levels of pTau181 were associated with AD, while Aβ42/Aβ40 had minimal differences. Correspondingly, pTau181 had a greater predictive value than Aβ42/Aβ40; however, the area under the curve differed between cohorts.DISCUSSIONpTau181 as a plasma biomarker for clinical AD is generalizable across genetic ancestries, but its predictive value may vary. Combining genomic and biomarker data from diverse individuals will increase understanding of genetic risk and refine clinical diagnoses.HighlightsThis is a diverse ancestry study of plasma biomarkers for AD.Plasma biomarkers were assessed in African Americans, Caribbean Hispanics, and Peruvians.Biomarker levels were consistent across the diverse cohorts.Plasma phosphorylated tau was higher in AD in all cohorts.Plasma biomarker findings in diverse cohorts largely generalize with existing European studies.