Sehrawat Anuradha, Zeng Xuemei, Abrahamson Eric E, Deek Rebecca A, Gogola Alexandra, Kamboh M Ilyas, Pascoal Tharick A, Villemagne Victor L, Lopez Oscar L, Ikonomovic Milos D, Snitz Beth E, Cohen Ann D, Karikari Thomas K
Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Geriatric Research Education and Clinical Center, VA Pittsburgh HS, Pittsburgh, PA, 15240, USA.
medRxiv. 2025 May 6:2025.05.03.25326526. doi: 10.1101/2025.05.03.25326526.
Most available p-tau217 immunoassays have similar performances. It is unclear if this is due to the use of the same antibody (the "ALZpath antibody"). We established and evaluated a novel p-tau217 assay that employs an alternative antibody, and benchmarked the results against ALZpath-p-tau217.
Following development and analytical validation of the University of Pittsburgh ("Pitt-p-tau217") method, clinical verification was performed in three independent cohorts (n=363).
Pitt-p-tau217 demonstrated high between-run stability, linearity, and specificity. Clinically, Pitt-p-tau217 differentiated neuropathologically confirmed mutation carriers from controls with AUC=0.94, and Aβ-PET-positive from Aβ-PET-negative cognitively normal older adults with AUC up to 0.84, equivalent to ALZpath-p-tau217 results. Both Pitt-p-tau217 and ALZpath-p-tau217 were elevated in tau-PET-positive versus tau-PET-negative participants (P=0.06; AUC=0.71 for both). Between-assay correlations were up to 0.93.
The new Pitt-p-tau217 assay exhibits high and reproducible classification accuracies for identifying individuals with biological evidence of AD, equivalent to the widely used ALZpath-p-tau217.
大多数现有的p-tau217免疫测定法具有相似的性能。目前尚不清楚这是否是由于使用了相同的抗体（“ALZpath抗体”）。我们建立并评估了一种采用替代抗体的新型p-tau217测定法，并将结果与ALZpath-p-tau217进行了对比。
在匹兹堡大学（“Pitt-p-tau217”）方法开发和分析验证之后，在三个独立队列（n = 363）中进行了临床验证。
Pitt-p-tau217表现出较高的批间稳定性、线性和特异性。在临床上，Pitt-p-tau217能够将经神经病理学证实的突变携带者与对照组区分开来，曲线下面积（AUC）= 0.94，并且能够将淀粉样蛋白β（Aβ）正电子发射断层扫描（PET）阳性与Aβ-PET阴性的认知正常老年人区分开来，AUC高达0.84，与ALZpath-p-tau217的结果相当。在tau-PET阳性与tau-PET阴性参与者中，Pitt-p-tau217和ALZpath-p-tau217均升高（P = 0.06；两者的AUC均为0.71）。测定间的相关性高达0.93。
新的Pitt-p-tau217测定法在识别具有阿尔茨海默病生物学证据的个体方面表现出高且可重复的分类准确性，与广泛使用的ALZpath-p-tau217相当。
