Tau pathology spread into neocortex indicates a transition from healthy aging to Alzheimer's disease (AD). Connectivity between tau epicenters and later accumulating regions of cortex has been proposed as a mechanism of tau spread, but how this relationship changes with greater AD pathology burden or genotype is not understood. We investigated tau accumulation in two key regions, precuneus and inferior temporal cortex, using resting state functional connectivity (rsFC) and longitudinal PET imaging from a multicohort sample of cognitively unimpaired older adults. We examined how baseline tau PET, Aβ PET, and ApoE4 genotype status interact with rsFC between hippocampus and these downstream regions to predict rate of tau accumulation in neocortex. We found that the 3‐way interaction between connectivity, baseline tau, and baseline Aβ or ApoE4 status was associated with neocortical tau accumulation in precuneus and inferior temporal cortex. In addition, baseline tau, Aβ, and ApoE4 status also moderated the association between connectivity and rate of memory decline. Together, these results suggest that the extent and distribution of future tau accumulation may be predicted by the interaction of baseline connectivity, AD pathology, and genetic risk.
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机译：Tau 病理扩散到新皮层表明从健康衰老过渡到阿尔茨海默病 （AD）。tau 震中和后来的皮层积累区域之间的连接已被提出作为 tau 传播的一种机制，但这种关系如何随着 AD 病理负担或基因型的增加而变化尚不清楚。我们使用静息态功能连接 （rsFC） 和来自认知未受损老年人多队列样本的纵向 PET 成像研究了楔前叶和颞下皮层两个关键区域的 tau 积累。我们检查了基线 tau PET 、 Aβ PET 和 ApoE4 基因型状态如何与海马和这些下游区域之间的 rsFC 相互作用，以预测新皮层中 tau 积累的速率。我们发现连接性、基线 tau 和基线 Aβ 或 ApoE4 状态之间的 3 向相互作用与楔前叶和颞下皮层的新皮层 tau 积累有关。此外，基线 tau 、 Aβ 和 ApoE4 状态也调节了连接性与记忆下降速度之间的关联。总之，这些结果表明，未来 tau 积累的程度和分布可以通过基线连通性、 AD 病理学和遗传风险的相互作用来预测。
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