Pandey Neetesh, Yang Zikun, Cieza Basilio, Reyes-Dumeyer Dolly, Kang Min Suk, Montesinos Rosa, Soto-Añari Marcio, Custodio Nilton, Honig Lawrence S, Tosto Giuseppe
Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.
The Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.
Alzheimers Res Ther. 2025 Jan 2;17(1):1. doi: 10.1186/s13195-024-01655-w.
Blood-based Alzheimer's disease (AD) biomarkers have been increasingly employed for diagnostic, prognostic, and therapeutic monitoring purposes, due to accuracy in distinguishing AD pathophysiologic process. Compared to other p-tau isoforms, plasma p-tau217 exhibits stronger associations with AD hallmarks in CSF and brain. However, most studies have been conducted in non-Hispanic Whites, limiting our understanding of the performances and utility of these biomarkers across ethnicities.
We examined a cohort of Peruvians from the GAPP study, a recently established cohort of Peruvian mestizos from Lima and indigenous groups from Southern Peru (Aymaras and Quechuas). We tested plasma levels of p-tau using the Quanterix Simoa ALZpathp-tau217 assay in 525 samples and tested the association between p-tau217 and clinical diagnosis (healthy controls n = 234 vs. AD n = 113) using generalized mixed regression models, adjusting for sex, age, education, APOE-e4 allele (fixed effects) and study site (random effect). We also tested biomarker levels in MCI (n = 178) vs. other groups. The receiver operating characteristics area under the curve (ROC-AUC) was used to evaluate the biomarker's classification performances.
Participants showed on average 80% Native American ancestry. p-tau217 was significantly associated with AD (β = 2.61, 95%CI = 0.61-4.29) and its levels were inversely correlated with cognitive performances; p-tau217 levels did not differ between controls and MCI (p-value > 0.05). p-tau217 levels were higher in participants carrying at least one APOE-e4 allele (OR = 2.31, 95%CI = 1.85-2.90). The ROC-AUC for p-tau217 was estimated at 82.82% in the fully adjusted model.
To our knowledge, this is the largest study conducted in a South American cohort phenotyped for AD with available p-tau217. Most investigations have previously focused on highly selected cohorts with established AD-endophenotypes (CSF biomarkers, autopsy report, PET etc.), while data on cohorts with clinical assessment are currently lacking, especially in non-European populations.
基于血液的阿尔茨海默病（AD）生物标志物因其在区分AD病理生理过程方面的准确性，越来越多地用于诊断、预后和治疗监测目的。与其他p-tau亚型相比，血浆p-tau217与脑脊液和大脑中的AD特征具有更强的相关性。然而，大多数研究是在非西班牙裔白人中进行的，这限制了我们对这些生物标志物在不同种族中的性能和效用的理解。
我们研究了来自GAPP研究的一组秘鲁人，这是一个最近建立的来自利马的秘鲁混血儿和来自秘鲁南部的土著群体（艾马拉人和克丘亚人）的队列。我们使用Quanterix Simoa ALZpath p-tau217检测法检测了525份样本中的p-tau血浆水平，并使用广义混合回归模型测试了p-tau217与临床诊断（健康对照n = 234 vs. AD n = 113）之间的关联，对性别、年龄、教育程度、APOE-e4等位基因（固定效应）和研究地点（随机效应）进行了调整。我们还测试了轻度认知障碍（MCI，n = 178）与其他组之间的生物标志物水平。曲线下面积（ROC-AUC）用于评估生物标志物的分类性能。
参与者平均有80%的美洲原住民血统。p-tau217与AD显著相关（β = 2.61，95%CI = 0.61 - 4.29），其水平与认知能力呈负相关；对照组和MCI之间的p-tau217水平没有差异（p值> 0.05）。携带至少一个APOE-e4等位基因的参与者的p-tau217水平更高（OR = 2.31，95%CI = 1.85 - 2.90）。在完全调整的模型中，p-tau217的ROC-AUC估计为82.82%。
据我们所知，这是在具有可用p-tau217的南美AD表型队列中进行的最大规模研究。以前大多数研究都集中在具有既定AD内表型（脑脊液生物标志物、尸检报告、PET等）的高度选择的队列上，而目前缺乏关于具有临床评估的队列的数据，特别是在非欧洲人群中。
