[ 18 F]-Flortaucipir positron emission tomography (PET) is considered a good biomarker of Alzheimer’s disease. However, it is unknown how flortaucipir is associated with the distribution of tau across brain regions and how these associations are influenced by amyloid-β. It is also unclear whether flortaucipir can detect tau in definite primary age–related tauopathy (PART). We identified 248 individuals at Mayo Clinic who had undergone [ 18 F]-flortaucipir PET during life, had died, and had undergone an autopsy, 239 cases of which also had amyloid-β PET. We assessed nonlinear relationships between flortaucipir uptake in nine medial temporal and cortical regions, Braak tau stage, and Thal amyloid-β phase using generalized additive models. We found that flortaucipir uptake was greater with increasing tau stage in all regions. Increased uptake at low tau stages in medial temporal regions was only observed in cases with a high amyloid-β phase. Flortaucipir uptake linearly increased with the amyloid-β phase in medial temporal and cortical regions. The highest flortaucipir uptake occurred with high Alzheimer’s disease neuropathologic change (ADNC) scores, followed by low-intermediate ADNC scores, then PART, with the entorhinal cortex providing the best differentiation between groups. Flortaucipir PET had limited ability to detect PART, and imaging-defined PART did not correspond with pathologically defined PART. In summary, spatial patterns of flortaucipir mirrored the histopathological tau distribution, were influenced by the amyloid-β phase, and were useful for distinguishing different ADNC scores and PART.

中文翻译：

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Flortaucipir PET 揭示了原发性年龄相关 tau 蛋白病和阿尔茨海默病中 tau 蛋白和淀粉样蛋白-β 之间的关系


[ 18 F]-Flortaucipir 正电子发射断层扫描（PET）被认为是阿尔茨海默病的良好生物标志物。然而，目前尚不清楚弗洛托西吡如何与 tau 蛋白在大脑区域的分布相关，以及这些关联如何受到 β 淀粉样蛋白的影响。目前还不清楚弗洛托西吡能否在确定的原发性年龄相关 tau 病 (PART) 中检测到 tau。我们在 Mayo Clinic 确定了 248 名生前接受过 [ 18 F]-flortaucipir PET、死亡并接受尸检的个体，其中 239 例也接受了淀粉样蛋白-β PET。我们使用广义相加模型评估了九个内侧颞叶和皮质区域、Braak tau 阶段和 Thal 淀粉样蛋白-β 阶段弗洛托西吡摄取之间的非线性关系。我们发现，随着所有区域 tau 阶段的增加，flortaucipir 的吸收量更大。仅在高淀粉样蛋白-β相的病例中观察到内侧颞区低tau阶段的摄取增加。弗洛托西吡的摄取随着内侧颞叶和皮质区域的淀粉样蛋白-β相线性增加。最高的弗洛托西吡摄取发生在阿尔茨海默氏病神经病理变化 (ADNC) 评分较高的情况下，其次是 ADNC 中低评分的情况，然后是 PART，其中内嗅皮层提供了组间的最佳区分。 Flortaucipir PET 检测 PART 的能力有限，并且影像学定义的 PART 与病理学定义的 PART 不一致。总之，flortaucipir 的空间模式反映了组织病理学 tau 分布，受淀粉样蛋白-β 相的影响，有助于区分不同的 ADNC 评分和 PART。