Piura Yoav D, Figdore Daniel J, Lachner Christian, Bornhorst Joshua, Algeciras-Schimnich Alicia, Graff-Radford Neill R, Day Gregory S
Department of Neurology, Mayo Clinic in Florida, Jacksonville, Florida, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Alzheimers Dement. 2025 Jun;21(6):e70316. doi: 10.1002/alz.70316.
Plasma biomarkers of Alzheimer's disease (AD) represent accessible alternatives to positron emission tomography (PET) and cerebrospinal fluid (CSF)-based biomarkers in well-characterized cohorts. It remains to be determined whether performance is maintained in outpatient clinics comprised of patients with multiple causes of cognitive impairment.
Plasma phosphorylated tau217 (p-tau217) and amyloid beta (Aβ) 42/40 were measured in 509 patients evaluated in a tertiary-care memory clinic. Biomarker performance was compared across diagnoses, referencing established cutpoints for positive and negative biomarkers.
Plasma p-tau217 distinguished patients with diagnoses of symptomatic AD with 95% sensitivity and 82% specificity. Integration of Aβ42 measurements (p-tau217/Aβ42) incrementally improved specificity (86%). Plasma p-tau217 and p-tau217/Aβ42 concentrations closely associated with established CSF biomarkers of AD (area under the curve [AUC]: 0.94 and 0.96, respectively). Reduced kidney function associated with elevated plasma p-tau217 and p-tau217/Aβ42 concentrations in patients without AD (referencing CSF biomarkers).
Plasma p-tau217 and p-tau217/Aβ42 concentrations demonstrated robust diagnostic performance in a heterogeneous clinical cohort; interpretation requires consideration of kidney function.
Plasma phosphorylated tau217 (p-tau217) reliably identified clinic patients with Alzheimer's disease. A two-cutpoint strategy yielded definitive results in 86% of patients. Integration of plasma amyloid beta (Aβ; p-tau217/Aβ42) minimally improved diagnostic performance. Plasma p-tau217 levels were increased in patients with kidney dysfunction.
在特征明确的队列中，阿尔茨海默病（AD）的血浆生物标志物是正电子发射断层扫描（PET）和基于脑脊液（CSF）的生物标志物之外的可获取替代物。在由多种认知障碍病因患者组成的门诊中，其性能是否能维持仍有待确定。
在一家三级医疗记忆门诊评估的509例患者中测量了血浆磷酸化tau217（p-tau217）和淀粉样β蛋白（Aβ）42/40。根据已确定的生物标志物阳性和阴性切点，比较了不同诊断的生物标志物性能。
血浆p-tau217对有症状AD诊断患者的区分敏感度为95%，特异度为82%。整合Aβ42测量值（p-tau217/Aβ42）可逐步提高特异度（86%）。血浆p-tau217和p-tau217/Aβ42浓度与已确定的AD脑脊液生物标志物密切相关（曲线下面积[AUC]分别为0.94和0.96）。在无AD患者中，肾功能降低与血浆p-tau217和p-tau217/Aβ42浓度升高相关（参考脑脊液生物标志物）。
血浆p-tau217和p-tau217/Aβ42浓度在异质性临床队列中表现出强大的诊断性能；解释时需要考虑肾功能。
血浆磷酸化tau217（p-tau217）可靠地识别出临床AD患者。双切点策略在86%的患者中得出明确结果。整合血浆淀粉样β蛋白（Aβ；p-tau217/Aβ42）对诊断性能的改善极小。肾功能不全患者的血浆p-tau217水平升高。
