PURPOSE The abnormal deposition of tau begins before the onset of clinical symptoms and seems to target specific brain networks. The aim of this study is to identify the spatial patterns of tau deposition in cognitively normal older adults and assess whether they are related to amyloid-β (Aβ), APOE, sex, and longitudinal cognitive decline. METHODS We included 114 older adults with cross-sectional flortaucipir (FTP) and Pittsburgh Compound-B PET in addition to longitudinal cognitive testing. A voxel-wise independent component analysis was applied to FTP images to identify the spatial patterns of tau deposition. We then assessed whether tau within these patterns differed by Aβ status, APOE genotype, and sex. Linear mixed effects models were built to test whether tau in each component predicted cognitive decline. Finally, we ordered the spatial components based on the frequency of high tau deposition to model tau spread. RESULTS We found 10 biologically plausible tau patterns in the whole sample. There was greater tau in medial temporal, occipital, and orbitofrontal components in Aβ-positive compared with Aβ-negative individuals; in the parahippocampal component in ε3ε3 compared with ε2ε3 carriers; and in temporo-parietal and anterior frontal components in women compared with men. Higher tau in temporal and frontal components predicted longitudinal cognitive decline in memory and executive functions, respectively. Tau deposition was most frequently observed in medial temporal and ventral cortical areas, followed by lateral and primary areas. CONCLUSIONS These findings suggest that the spatial patterns of tau in asymptomatic individuals are clinically meaningful and are associated with Aβ, APOE ε2ε3, sex and cognitive decline. These patterns could be used to predict the regional spread of tau and perform in vivo tau staging in older adults.

中文翻译：

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tau 沉积的空间模式与老年人的淀粉样蛋白、ApoE、性别和认知能力下降有关。

目的 tau 的异常沉积在临床症状出现之前就开始了，并且似乎针对特定的大脑网络。本研究的目的是确定认知正常的老年人中 tau 沉积的空间模式，并评估它们是否与淀粉样蛋白-β (Aβ)、APOE、性别和纵向认知衰退有关。方法 我们纳入了 114 名老年人，除了纵向认知测试外，还进行了横断面 flortaucipir (FTP) 和 Pittsburgh Compound-B PET。对 FTP 图像应用体素独立成分分析，以确定 tau 沉积的空间模式。然后我们评估了这些模式中的 tau 是否因 Aβ 状态、APOE 基因型和性别而不同。建立了线性混合效应模型来测试每个成分中的 tau 蛋白是否预测认知能力下降。最后，我们根据高 tau 沉积的频率对空间成分进行排序，以模拟 tau 扩散。结果 我们在整个样本中发现了 10 种生物学上合理的 tau 模式。与 Aβ 阴性个体相比，Aβ 阳性个体的内侧颞叶、枕叶和眶额叶成分中有更多的 tau；在 ε3ε3 与 ε2ε3 载体中的海马旁成分中；与男性相比，女性的颞顶叶和前额叶成分。时间和额叶成分中较高的 tau 分别预测记忆和执行功能的纵向认知衰退。Tau 沉积最常见于内侧颞叶和腹侧皮质区域，其次是外侧和主要区域。结论 这些发现表明，无症状个体中 tau 的空间模式具有临床意义，并且与 Aβ、APOE ε2ε3、性别和认知能力下降有关。这些模式可用于预测 tau 的区域传播并在老年人中进行体内 tau 分期。