Brodman Shayna T, Heaton Nicholas, Triana-Baltzer Gallen, Zeng Xuemei, Gogola Alexandra, Kamboh M Ilyas, Villemagne Victor L, Lopez Oscar L, Kolb Hartmuth, Deek Rebecca A, Cohen Ann D, Karikari Thomas K
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Department of Biostatistics and Health Data Science, School of Public Health, University of Pittsburgh, Pittsburgh, PA 15213, USA.
medRxiv. 2025 Jul 11:2025.07.10.25331312. doi: 10.1101/2025.07.10.25331312.
We evaluated plasma biomarker association with, and classification accuracies for, Aβ-PET and cortical thickness in the biracial HCP-CoBRA cohort (53% B/AA and 47% NHW).
In n=218 participants (age 62 [range: 57-71] years, 65% female and 15% Aβ PET-positive), plasma biomarkers (p-tau181, p-tau217, p-tau231, GFAP, NfL, Aβ42/Aβ40) were compared to Aβ-PET and MRI neuroimaging indicators.
P-tau217 (Janssen and ALZpath [AUCs=0.915-0.919]) had high sensitivity and specificity (>85%) for Aβ-PET status. All biomarkers except p-tau231 ruled out Aβ-pathology (NPV>95%) but only Janssen p-tau217+ was good for confirmation (PPV=0.909). Plasma biomarkers performed poorly for predicting cortical thickness but were elevated according to joint Aβ-PET-neurodegeneration profiles. Biomarker accuracies for Aβ-PET positivity were unaffected by self-identified race, except ALZpath p-tau217(p=0.024). However, correlations with Aβ-PET varied by self-identified race.
P-tau217 is a promising tool for Alzheimer's disease-related Aβ pathology in older/middle-aged individuals. However, apparent race-related performances should be further studied.
我们在双种族的健康脑计划-大脑衰老研究联盟队列（53%为非裔美国人和非西班牙裔白人，47%为非西班牙裔白人）中评估了血浆生物标志物与淀粉样蛋白正电子发射断层扫描（Aβ-PET）及皮质厚度的相关性和分类准确性。
在n = 218名参与者（年龄62岁[范围：57 - 71岁]，65%为女性，15%为Aβ PET阳性）中，将血浆生物标志物（磷酸化tau蛋白181、磷酸化tau蛋白217、磷酸化tau蛋白231、胶质纤维酸性蛋白、神经丝轻链、Aβ42/Aβ40）与Aβ-PET和磁共振成像（MRI）神经影像学指标进行比较。
磷酸化tau蛋白217（杨森公司和阿尔茨海默病神经影像学计划[AUC值 = 0.915 - 0.919]）对Aβ-PET状态具有高敏感性和特异性（>85%）。除磷酸化tau蛋白231外，所有生物标志物均排除了Aβ病理（阴性预测值>95%），但只有杨森公司的磷酸化tau蛋白217呈阳性有助于确诊（阳性预测值 = 0.909）。血浆生物标志物在预测皮质厚度方面表现不佳，但根据联合的Aβ-PET-神经退行性变图谱会升高。Aβ-PET阳性的生物标志物准确性不受自我认定种族的影响，但阿尔茨海默病神经影像学计划的磷酸化tau蛋白217除外（p = 0.024）。然而，与Aβ-PET的相关性因自我认定种族而异。
磷酸化tau蛋白217是用于老年/中年个体阿尔茨海默病相关Aβ病理的一种有前景的工具。然而，明显的种族相关表现应进一步研究。
