[¹⁸F]Flortaucipir is an FDA-approved tau-PET tracer that is increasingly utilized in clinical settings for the diagnosis of Alzheimer’s disease. Still, a large-scale comparison of the in vivo PET uptake to quantitative post-mortem tau pathology and to other co-pathologies is lacking. Here, we examined the correlation between in vivo [¹⁸F]flortaucipir PET uptake and quantitative post-mortem tau pathology in corresponding brain regions from the AVID A16 end-of-life study (n = 63). All participants underwent [¹⁸F]flortaucipir PET scans prior to death, followed by a detailed post-mortem neuropathological examination using AT8 (tau) immunohistochemistry. Correlations between [¹⁸F]flortaucipir standardized uptake value ratios (SUVRs) and AT8 immunohistochemistry were assessed across 18 regions-of-interest (ROIs). To assess [¹⁸F]flortaucipir specificity and level of detection for tau pathology, correlations between [¹⁸F]flortaucipir SUVR and neuritic plaque score and TDP-43 stage were also computed and retention was further assessed in individuals with possible primary age-related tauopathy (PART), defined as Thal phase ≤ 2 and Braak stage I–IV. We found modest-to-strong correlations between in vivo [¹⁸F]flortaucipir SUVR and post-mortem tau pathology density in corresponding brain regions in all neocortical regions analyzed (rho-range = 0.61–0.79, p < 0.0001 for all). The detection threshold of [¹⁸F]flortaucipir PET was determined to be 0.85% of surface area affected by tau pathology in a temporal meta-ROI, and 0.15% in a larger cortical meta-ROI. No significant associations were found between [¹⁸F]flortaucipir SUVRs and post-mortem tau pathology in individuals with possible PART. Further, there was no correlation observed between [¹⁸F]flortaucipir and level of amyloid-β neuritic plaque load (rho-range = – 0.16–0.12; p = 0.48–0.61) or TDP-43 stage (rho-range = – 0.10 to – 0.30; p = 0.18–0.65). In conclusion, our in vivo vs post-mortem study shows that the in vivo [¹⁸F]flortaucipir PET signal primarily reflects tau pathology, also at relatively low densities of tau proteinopathy, and does not bind substantially to tau neurites in neuritic plaques or in individuals with PART.

[ ¹⁸ F]Flortaucipir 是 FDA 批准的 tau-PET 示踪剂，越来越多地在临床环境中用于诊断阿尔茨海默病。尽管如此，仍缺乏体内 PET 摄取与定量死后tau 病理学和其他共同病理学的大规模比较。在这里，我们检查了体内 [ ¹⁸ F]flortaucipir PET 摄取与来自 AVID A16 临终研究 ( n = 63) 的相应大脑区域的定量死后tau 病理学之间的相关性。所有参与者在死亡前均接受了 [ ¹⁸ F]flortaucipir PET 扫描，然后使用 AT8 (tau) 免疫组织化学进行详细的尸检神经病理学检查。在 18 个感兴趣区域 (ROI) 中评估了 [ ¹⁸ F]flortaucipir 标准化摄取值比率 (SUVR) 和 AT8 免疫组织化学之间的相关性。为了评估 [ ¹⁸ F]flortaucipir 特异性和 tau 病理学检测水平，还计算了 [ ¹⁸ F]flortaucipir SUVR 与神经炎斑块评分和 TDP-43 分期之间的相关性，并在可能患有原发性年龄相关 tau 病的个体中进一步评估保留情况（部分），定义为 Thal 期 ≤ 2 和 Braak I-IV 期。我们发现体内 [ ¹⁸ F]flortaucipir SUVR 与所有分析的新皮质区域相应脑区的死后tau 病理密度之间存在中等到强的相关性（rho 范围 = 0.61–0.79，p < 0.0001）。 [ ¹⁸ F]flortaucipir PET 的检测阈值被确定为在颞侧元 ROI 中受 tau 病理学影响的表面积的 0.85%，在较大的皮质元 ROI 中为 0.15%。 在可能患有 PART 的个体中，[ ¹⁸ F]flortaucipir SUVR 与死后tau 病理学之间没有发现显着关联。此外，[ ¹⁸ F]flortaucipir 与淀粉样蛋白-β 神经炎斑块负荷水平（rho 范围 = – 0.16–0.12； p = 0.48–0.61）或 TDP-43 分期（rho 范围 = – 0.10）之间没有观察到相关性。至 – 0.30； p = 0.18–0.65）。总之，我们的体内与死后研究表明，体内 [ ¹⁸ F]flortaucipir PET 信号主要反映 tau 病理学，而且 tau 蛋白病密度相对较低，并且基本上不与神经炎斑块或神经炎斑块中的 tau 神经突结合。具有 PART 的个人。