Progressive supranuclear palsy (PSP) is a neurodegenerative disorder characterized by neuroglial tau pathology. A new staging system for PSP pathology postmortem has been described and validated. We used a data-driven approach to test whether postmortem pathologic staging in PSP can be reproduced in vivo with ¹⁸F-flortaucipir PET. Methods: Forty-two patients with probable PSP and 39 controls underwent ¹⁸F-flortaucipir PET. Conditional inference tree analyses on regional binding potential values identified absent/present pathology thresholds to define in vivo staging. Following the postmortem staging approach for PSP pathology, we evaluated the combinations of absent/present pathology (or abnormal/normal PET signal) across all regions to assign each participant to in vivo stages. ANOVA was applied to analyze differences among means of disease severity between stages. In vivo staging was compared with postmortem staging in 9 patients who also had postmortem confirmation of the diagnosis and stage. Results: Stage assignment was estimable in 41 patients: 10, 26, and 5 patients were classified in stage I/II, stage III/IV, and stage V/VI, respectively, whereas 1 patient was not classifiable. Explorative substaging identified 2 patients in stage I, 8 in stage II, 9 in stage III, 17 in stage IV, and 5 in stage V. However, the nominal ¹⁸F-flortaucipir--derived stage was not associated with clinical severity and was not indicative of pathology staging postmortem. Conclusion: ¹⁸F-flortaucipir PET in vivo does not correspond to neuropathologic staging in PSP. This analytic approach, seeking to mirror in vivo neuropathology staging with PET-to-autopsy correlational analyses, might enable in vivo staging with next-generation tau PET tracers; however, further evidence and comparisons with postmortem data are needed.

进行性核上性麻痹 (PSP) 是一种以神经胶质 tau 蛋白病理学为特征的神经退行性疾病。描述并验证了一种新的 PSP 病理学尸检分期系统。我们使用数据驱动的方法来测试 PSP 的死后病理分期是否可以使用¹⁸ F-flortaucipir PET 在体内重现。方法： 42 名可能患有 PSP 的患者和 39 名对照患者接受了¹⁸ F-flortaucipir PET。对区域结合电位值的条件推理树分析确定了不存在/存在的病理阈值以定义体内分期。按照 PSP 病理学的死后分期方法，我们评估了所有区域中不存在/存在的病理学（或异常/正常 PET 信号）的组合，以将每个参与者分配到体内阶段。应用方差分析来分析不同阶段疾病严重程度平均值的差异。对 9 名患者进行了体内分期与死后分期的比较，这些患者的诊断和分期也经过死后确认。结果： 41 名患者的分期是可估计的：分别有 10、26 和 5 名患者被分类为 I/II 期、III/IV 期和 V/VI 期，而 1 名患者无法分类。探索性分期确定了 2 名患者处于 I 期、8 名处于 II 期、9 名处于 III 期、17 名处于 IV 期和 5 名处于 V 期。然而，名义¹⁸ F-flortaucipir 衍生分期与临床严重程度无关，并且不代表尸检病理分期。结论： ¹⁸ F-flortaucipir 体内 PET 与 PSP 的神经病理学分期不相符。这种分析方法旨在通过 PET 与尸检相关分析来反映体内神经病理学分期，可能能够使用下一代 tau PET 示踪剂进行体内分期；然而，还需要进一步的证据以及与尸检数据的比较。