Imaging Tauopathy in the Dominanatly Inherited Alzheimer Network (DIAN)

摘要/项目摘要 在这项建议中，我们通过以下方式探索从临床前到症状性阿尔茨海默病(AD)的过渡 将新的tau成像示踪剂([18F]-AV-1451)整合到Domantly富含生物标记物的方案中 遗传性阿尔茨海默病网络(DIAN)。我们利用DIAN的现有基础设施并与 Avid RadiopPharmticticals在这一独特的队列中启动tau正电子发射断层扫描(PET)成像。 Dian为AD由临床前阶段组成的假说提供了基本支持 β-淀粉样蛋白(A-β)斑块堆积和tau神经原纤维缠结(NFT)逐渐导致神经元 功能障碍和认知障碍。然而，在我们对时间和时间的理解中，仍然存在关键差距 Aβ和tau之间的空间相互作用发生在从临床前症状到临床症状的转变过程中。 这项提议通过三个目标回答了这些基本问题。目的1研究时间动力学 Tau沉积(使用AV-1451)与症状出现前的估计年限(EYO)和现有的 DIAN中的生物标志物(包括脑脊液、神经成像和认知能力)。目标2研究 Tau沉积的空间(局部和分布)变化(使用AV-1451)。AIM 3研究了 体内tau沉积(使用AV-1451)与神经病理学的关系。常染色体独有 显性AD(ADAD)，DIAN参与者的年轻年龄消除了与潜在年龄相关的重叠 神经病理学或紧张症(部分)。我们的总体假设是，从认知正常到 神经影像生物标记物，特别是AV-1451PET可以准确预测症状性AD。 这一建议的结果是我们理解PET tau不仅仅是一种诊断指标的基础 它不仅是评估ADAD未来干预措施临床疗效的一个治疗标记物。

ABSTRACT/PROJECT SUMMARY In this proposal we explore the transition from preclinical to symptomatic Alzheimer disease (AD) by incorporating the novel tau imaging tracer ([18F]-AV-1451) within the biomarker-rich protocol of the Dominantly Inherited Alzheimer Network (DIAN). We leverage the existing infrastructure of DIAN and a collaboration with Avid Radiopharmaceuticals to initiate tau positron emission tomography (PET) imaging in this unique cohort. DIAN provides fundamental support to the hypothesis that AD consists of a preclinical stage in which accumulation of beta-amyloid (Aβ) plaques and tau neurofibrillary tangle (NFT) gradually lead to neuronal dysfunction and cognitive impairment. However, key gaps remain in our understanding of the temporal and spatial interactions that occur between Aβ and tau during the transition from preclinical to clinical symptoms. This proposal answers these fundamental questions through three aims. Aim 1 studies the temporal dynamics of tau deposition (using AV-1451) in relation to estimated years to symptom onset (EYO) and existing biomarkers in DIAN (including cerebrospinal fluid, neuroimaging, and cognitive performance). Aim 2 studies the spatial (both local and distributed) changes of tau deposition (using AV-1451). Aim 3 studies the relationship between in vivo tau deposition (using AV-1451) and neuropathology. Unique to autosomal dominant AD (ADAD), the young age of the DIAN participants eliminates overlap with potential age-related neuropathology or tauopathy (PART). Our overall hypothesis is that conversion from cognitively normal to symptomatic AD can be accurately predicted by neuroimaging biomarkers, in particular by AV-1451 PET. Results from this proposal are fundamental for our understanding of PET tau as not only a diagnostic indicator of disease but also a therapeutic marker to evaluate the clinical efficacy of future interventions in ADAD.