In this retrospective, cross-sectional diagnostic cohort study, we first developed P-tau217 cutoffs using site-specific and BioFINDER-2 training data, which were then tested in potential DMT candidates from Butler MAP (total n = 150). ROC analysis was used to calculate the area under the curve (AUC) and accuracy of P-tau217 interpretation strategies, using Aβ-PET/CSF testing as the standard of truth.
Potential DMT candidates at Butler MAP (n = 50), primarily diagnosed with mild cognitive impairment (n = 29 [58%]) or mild dementia (21 [42%]), were predominantly Aβ-positive (38 [76%]), and half (25 [50%]) were subsequently treated with aducanumab. Elevated P-tau217 predicted cerebral Aβ positivity in potential DMT candidates (AUC = 0.97 [0.92-1]), with diagnostic accuracy ranging from 0.88 (0.76-0.95, p = 0.028) to 0.96 (0.86-1, p < .001). When using site-specific cutoffs, a subset of DMT candidates (10%) exhibited borderline P-tau217 (between 0.273 and 0.399 pg/mL) that would have potentially required confirmatory testing.
This study, which included participants treated with aducanumab, confirms the utility of one- and two-cutoff strategies for interpreting plasma P-tau217 in assessing DMT eligibility. Using P-tau217 could potentially replace more invasive diagnostic methods, and all aducanumab-treated participants would have been deemed eligible based on P-tau217. However, false positives remain a concern, particularly when applying externally derived cutoffs that exhibited lower specificity which could have led to inappropriate treatment of Aβ-negative participants. Future research should focus on prospective validation of P-tau217 cutoffs to enhance their generalizability and inform standardized treatment decision-making across diverse populations.
方法:在本回顾性研究中,横断面诊断队列研究,我们首先使用特定站点和BioFINDER-2训练数据开发了P-tau217截止值,然后在来自ButlerMAP的潜在DMT候选物中进行测试(总n=150)。ROC分析用于计算曲线下面积(AUC)和P-tau217解释策略的准确性,使用Aβ-PET/CSF测试作为真理的标准。
结果:巴特勒MAP的潜在DMT候选者(n=50),主要诊断为轻度认知障碍(n=29[58%])或轻度痴呆(21[42%]),主要为Aβ阳性(38[76%]),一半(25[50%])随后接受了阿杜卡单抗治疗。P-tau217在潜在的DMT候选物中预测脑Aβ阳性(AUC=0.97[0.92-1]),诊断准确性范围从0.88(0.76-0.95,p=0.028)到0.96(0.86-1,p<.001)。使用特定于站点的截止值时,一部分DMT候选物(10%)显示P-tau217临界线(0.273~0.399pg/mL),可能需要进行验证性测试.
结论:这项研究,其中包括接受aducanumab治疗的参与者,确认了一截止和两截止策略在评估DMT合格性时解释血浆P-tau217的实用性。使用P-tau217可能会取代更具侵入性的诊断方法,根据P-tau217,所有接受aducanumab治疗的参与者均被视为符合条件.然而,假阳性仍然是一个令人担忧的问题,特别是当应用外部来源的显示较低特异性的截止值时,这可能导致对Aβ阴性参与者的不适当治疗。未来的研究应该集中在P-tau217截止值的前瞻性验证上,以增强其普遍性,并为不同人群的标准化治疗决策提供信息。