Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Faculty of Medicine, Lund University, Lund, Sweden.
Department of Neurology, Skåne University Hospital, Lund, Sweden.
Acta Neuropathol. 2024 Sep 19;148(1):44. doi: 10.1007/s00401-024-02801-2.
[F]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 [F]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 [F]flortaucipir PET scans prior to death, followed by a detailed post-mortem neuropathological examination using AT8 (tau) immunohistochemistry. Correlations between [F]flortaucipir standardized uptake value ratios (SUVRs) and AT8 immunohistochemistry were assessed across 18 regions-of-interest (ROIs). To assess [F]flortaucipir specificity and level of detection for tau pathology, correlations between [F]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 [F]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 [F]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 [F]flortaucipir SUVRs and post-mortem tau pathology in individuals with possible PART. Further, there was no correlation observed between [F]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 [F]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.
[F]Flortaucipir 是一种经美国食品药品监督管理局批准的 tau-PET 示踪剂，越来越多地用于临床阿尔茨海默病的诊断。然而，体内 [F]flortaucipir PET 摄取与定量死后 tau 病理学和其他共病之间的大规模比较仍然缺乏。在这里，我们检查了来自 AVID A16 临终研究（n=63）的相应大脑区域的体内 [F]flortaucipir PET 摄取与定量死后 tau 病理学之间的相关性。所有参与者在死亡前都接受了 [F]flortaucipir PET 扫描，随后使用 AT8（tau）免疫组织化学进行详细的死后神经病理学检查。在 18 个感兴趣区域（ROI）中评估了 [F]flortaucipir 标准化摄取比值（SUVR）与 AT8 免疫组织化学之间的相关性。为了评估 [F]flortaucipir 对 tau 病理学的特异性和检测水平，还计算了 [F]flortaucipir SUVR 与神经原纤维缠结评分和 TDP-43 阶段之间的相关性，并进一步评估了可能的原发性年龄相关性 tau 病（PART）个体中的保留情况，定义为 Thal 阶段≤2 和 Braak 阶段 I-IV。我们发现，在所分析的所有新皮质区域中，体内 [F]flortaucipir SUVR 与死后 tau 病理学密度之间存在中等至强相关性（rho 范围为 0.61-0.79，p<0.0001）。在颞叶meta-ROI 中，[F]flortaucipir PET 的检测阈值确定为受 tau 病理学影响的表面积的 0.85%，在更大的皮质 meta-ROI 中为 0.15%。在可能的 PART 个体中，未发现 [F]flortaucipir SUVR 与死后 tau 病理学之间存在显著关联。此外，在 [F]flortaucipir 与淀粉样β神经原纤维缠结负荷水平（rho 范围为-0.16-0.12；p=0.48-0.61）或 TDP-43 阶段（rho 范围为-0.10 到-0.30；p=0.18-0.65）之间也没有观察到相关性。总之，我们的体内与死后研究表明，体内 [F]flortaucipir PET 信号主要反映 tau 病理学，即使在 tau 蛋白病的相对低密度下也是如此，并且不会与神经原纤维缠结中的 tau 神经突或 PART 个体中的 tau 神经突大量结合。
