Brainstem connectomes related to Alzheimer's disease

摘要 与内侧颞叶和其他皮质区域相比，脑干很少受到关注 阿尔茨海默病（AD）研究中。越来越多的证据来自各种神经病理学研究和最近 然而，更新的Braak分期表明，最早的tau病变可能发生在脑干核团 并传播到经内嗅皮质区域。虽然使用AV 1451示踪剂的tau PET成像正在出现， 作为测量皮质tau蛋白负荷的有力工具，由于分辨率较低， 和脱靶结合。另一方面，连接体成像技术的巨大进步使我们能够 以前所未有的细节研究大脑通路的完整性。使用多壳层扩散成像数据， 在人类连接组计划（HCP）中，我们开发了计算纤维取向的新工具， 分布（FOD）和房室模型。这些工具已成功应用于重建 挑战人类大脑中的纤维通路。在这个项目中，我们将利用尖端的连接体和tau蛋白 来自两项NIH资助的研究的PET成像数据和我们用于构建脑干图谱的新型分析算法 用于AD研究的连接体。我们的目标是开发能够提供连接的技术 脑干测量以补充来自PET成像的皮质tau负荷。新的脑干图谱 和相关的软件工具，我们将能够检查脑干和 AD病程中皮质萎缩。这些实验的结果将提供体内 关于AD前驱期tau病理学Braak分期的证据。此外，脑干 连接体将能够在体内映射神经递质特异性通路中的连接变化 及其与AD患者行为症状的关系。总的来说，该项目有三个具体目标：1。到 使用连接体成像数据开发与AD相关的脑干通路图谱。2.为了检验 AD中脑干核团和皮质tau病理学的连接性变化。3.为了研究行为与行为之间的关系， 症状和脑干连通性。本项目开发的所有地图集和软件工具将 免费分发给研究界。当我们开发这些地图集和工具来研究AD时， 在其他神经系统疾病的研究中也应该是有价值的，在这些疾病中，脑干起着重要的作用。 作用

Abstract Compared with the medial temporal lobe and other cortical regions, little attention has been paid to the brainstem in Alzheimer's disease (AD) research. Increasing evidence from various neuropathology studies and recently updated Braak staging, however, suggested that the earliest tau pathology may occur in the brainstem nuclei and propagate to trans-entorhinal cortical regions. While tau PET imaging with the AV1451 tracer is emerging as a powerful tool for measuring cortical tau burden, it is limited for studying the brainstem due to low resolution and off-target binding. On the other hand, great advances in connectome imaging techniques have enabled us to study the integrity of brain pathways with unprecedented detail. Using multi-shell diffusion imaging data from the Human Connectome Project (HCP), we have developed novel tools for computing the fiber orientation distributions (FODs) and compartment models. These tools have been successfully applied to reconstruct challenging fiber pathways in the human brain. In this project, we will leverage cutting-edge connectome and tau PET imaging data from two NIH-funded studies and our novel analysis algorithms to build atlases of brainstem connectomes for AD research. Our goal is to develop the enabling techniques that can provide connectivity measures of brainstem to complement cortical tau burdens from PET imaging. With the novel brainstem atlases and associated software tools developed in this project, we will be able to examine the relation of brainstem and cortical atrophy during the disease course of AD. The findings from such experiments will provide in vivo evidence about the Braak staging of tau pathology in the prodromal phase of AD. In addition, the brainstem connectomes will enable the in vivo mapping of the connectivity changes in neurotransmitter-specific pathways and their relation to behavior symptoms in AD patients. Overall there are three specific aims in this project: 1. To develop atlases of brainstem pathways related to AD using connectome imaging data. 2. To examine the relation of connectivity changes in brainstem nuclei and cortical tau pathology in AD. 3. To study the relation of behavioral symptoms and brainstem connectivity in AD. All atlases and software tools developed in this project will be distributed freely to the research community. While we develop these atlases and tools for studying AD, they should also be valuable in research about other neurological disorders where the brainstem plays an important role.